Molecules

11 pages, 1251 KiB

Open AccessArticle

DNA Three Way Junction Core Decorated with Amino Acids-Like Residues-Synthesis and Characterization

by Claudia Addamiano, Béatrice Gerland^*, Corinne Payrastre

and Jean-Marc Escudier^*

Laboratoire de Synthèse et Physico-Chimie de Molécules d′Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 Route de Narbonne, Cedex 9, Toulouse 31062, France

Molecules 2016, 21(9), 1082; https://doi.org/10.3390/molecules21091082 - 23 Aug 2016

Cited by 5 | Viewed by 8073

Abstract

Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post [...] Read more.

Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post synthetic CuACC reaction with either protected imidazolyl-, hydroxyl- or carboxyl-azide. Structural impacts of 5′-C(S)-functionalization were investigated to evaluate how 3WJ flexibility/stability is affected. Full article

(This article belongs to the Collection New Frontiers in Nucleic Acid Chemistry)

▼ Show Figures

Graphical abstract

26 pages, 11541 KiB

Open AccessReview

Plant Cell Cancer: May Natural Phenolic Compounds Prevent Onset and Development of Plant Cell Malignancy? A Literature Review

by Hassan Rasouli^1,†

, Mohammad Hosein Farzaei^1,2,†, Kamran Mansouri¹, Sara Mohammadzadeh¹ and Reza Khodarahmi^1,3,*

¹ Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714967346, Iran

² Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714967346, Iran

³ Nano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714967346, Iran

Molecules 2016, 21(9), 1104; https://doi.org/10.3390/molecules21091104 - 23 Aug 2016

Cited by 68 | Viewed by 14042

Abstract

Phenolic compounds (PCs) are known as a chemically diverse category of secondary and reactive metabolites which are produced in plants via the shikimate-phenylpropanoid pathways. These compounds—ubiquitous in plants—are an essential part of the human diet, and are of considerable interest due to their [...] Read more.

Phenolic compounds (PCs) are known as a chemically diverse category of secondary and reactive metabolites which are produced in plants via the shikimate-phenylpropanoid pathways. These compounds—ubiquitous in plants—are an essential part of the human diet, and are of considerable interest due to their antioxidant properties. Phenolic compounds are essential for plant functions, because they are involved in oxidative stress reactions, defensive systems, growth, and development. A large body of cellular and animal evidence carried out in recent decades has confirmed the anticancer role of PCs. Phytohormones—especially auxins and cytokinins—are key contributors to uncontrolled growth and tumor formation. Phenolic compounds can prevent plant growth by the endogenous regulation of auxin transport and enzymatic performance, resulting in the prevention of tumorigenesis. To conclude, polyphenols can reduce plant over-growth rate and the development of tumors in plant cells by regulating phytohormones. Future mechanistic studies are necessary to reveal intracellular transcription and transduction agents associated with the preventive role of phenolics versus plant pathological malignancy cascades. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

10 pages, 1977 KiB

Open AccessArticle

Elucidation of Differential Accumulation of 1-Phenylethanol in Flowers and Leaves of Tea (Camellia sinensis) Plants

by Fang Dong^1,†, Ying Zhou^2,†, Lanting Zeng², Qiyuan Peng², Yiyong Chen², Ling Zhang², Xinguo Su^1,*, Naoharu Watanabe³ and Ziyin Yang^2,*

¹ Guangdong Food and Drug Vocational College, Longdongbei Road 321, Tianhe District, Guangzhou 510520, China

² Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, China

³ Graduate School of Science and Technology, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561, Japan

Molecules 2016, 21(9), 1106; https://doi.org/10.3390/molecules21091106 - 23 Aug 2016

Cited by 17 | Viewed by 6416

Abstract

1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is [...] Read more.

1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is unknown. In the present study, enzymes in the last step leading from acetophenone to 1PE were isolated from tea flowers by traditional biochemical chromatography. The two types of partially purified enzymes were proposed to be responsible for formations of (R)-1PE and (S)-1PE, respectively. Tea leaves also contained such enzymes having equivalent activities with flowers. Stable isotope labeling experiments indicated that weak transformation from l-phenylalanine to acetophenone in leaves mainly resulted in little occurrence of 1PE in leaves. This study provided an example that differential distribution of some metabolites in plant tissues was not only determined by enzyme(s) in the last step of metabolite formation, but also can be due to substrate availability. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

▼ Show Figures

Figure 1

18 pages, 4336 KiB

Open AccessArticle

Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson’s Disease

by Nuramatjan Ablat^1,2, Deyong Lv^3,4, Rutong Ren^1,2, Yilixiati Xiaokaiti^2,5, Xiang Ma^1,2, Xin Zhao^1,2, Yi Sun^1,2

, Hui Lei^1,2, Jiamin Xu^1,2, Yingcong Ma², Xianrong Qi²

, Min Ye², Feng Xu², Hongbin Han^3,6,* and Xiaoping Pu^1,2,*

¹ Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

² State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China

³ Department of Radiology, Peking University Third Hospital, Beijing100191, China

⁴ Department of Radiology, Dongying People’s Hospital of Shandong, Dongying 257091, China

⁵ Department of Molecular and Cellular Pharmacology, School of Basic Medical Sciences, Peking University, Beijing100191, China

⁶ Beijing Key Lab of MRI Device and Technique, Peking University Third Hospital, Beijing 100191, China

Molecules 2016, 21(9), 1107; https://doi.org/10.3390/molecules21091107 - 24 Aug 2016

Cited by 68 | Viewed by 11097

Abstract

Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. [...] Read more.

Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

▼ Show Figures

Figure 1

13 pages, 1298 KiB

Open AccessArticle

Marine Toxin Okadaic Acid Affects the Immune Function of Bay Scallop (Argopecten irradians)

by Cheng Chi, Sib Sankar Giri, Jin Woo Jun, Hyoun Joong Kim, Saekil Yun, Sang Guen Kim and Se Chang Park^*

Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151742, Korea

Molecules 2016, 21(9), 1108; https://doi.org/10.3390/molecules21091108 - 24 Aug 2016

Cited by 29 | Viewed by 5778

Abstract

Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on [...] Read more.

Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the immune responses of bay scallop, Argopecten irradians. Various immunological parameters were assessed (total hemocyte counts (THC), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), and nitric oxide (NO) in the hemolymph of scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations of OA (50, 100, and 500 nM). Moreover, the expression of immune-system-related genes (CLT-6, FREP, HSP90, MT, and Cu/ZnSOD) was also measured. Results showed that ROS, MDA, and NO levels and LDH activity were enhanced after exposure to different concentrations of OA; however, both THC and GSH decreased between 24–48 hpe. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that exposure to OA had negative effects on immune system function, increased oxygenic stress, and disrupted metabolism of bay scallops. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

12 pages, 1195 KiB

Open AccessArticle

Stability, Antioxidant Capacity and Degradation Kinetics of Pelargonidin-3-glucoside Exposed to Ultrasound Power at Low Temperature

by Jianxia Sun^1,†, Zhouxiong Mei^1,2,†, Yajuan Tang², Lijun Ding¹, Guichuan Jiang³, Chi Zhang^1,2, Aidong Sun^4,* and Weibin Bai^2,*

¹ Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China

² Department of Food Science and Engineering, Jinan University, Guangzhou 510632, China

³ Department of Food Science and Engineering, Shandong Agriculture and Engineering University, Jinan 250199, China

⁴ College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China

Molecules 2016, 21(9), 1109; https://doi.org/10.3390/molecules21091109 - 24 Aug 2016

Cited by 31 | Viewed by 6298

Abstract

As an alternative preservation method to thermal treatment, ultrasound is a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, recently literature indicated that anthocyanin degradation occurred when high amplitude ultrasound was applied to juice. This work mainly studied the [...] Read more.

As an alternative preservation method to thermal treatment, ultrasound is a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, recently literature indicated that anthocyanin degradation occurred when high amplitude ultrasound was applied to juice. This work mainly studied the effect of ultrasound on the stability and antioxidant capacity of pelargonidin-3-glucoside (Pg-3-glu) and the correlation between anthocyanin degradation and •OH generation in a simulated system. Results indicated that the spectral intensities of Pg-3-glu decreased with increasing ultrasound power (200–500 W) and treatment time (0–60 min). The degradation trend was consistent with first-order reaction kinetics (R² > 0.9100). Further study showed that there was a good linear correlation between Pg-3-glu degradation and •OH production (R² = 0.8790), which indicated the important role of •OH in the degradation of anthocyanin during ultrasound exposure. Moreover, a decrease in the antioxidant activity of solution(s) containing Pg-3-glu as evaluated by the DPPH and FRAP methods was observed after ultrasound treatment. Full article

▼ Show Figures

Graphical abstract

10 pages, 1382 KiB

Open AccessArticle

In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats

by Jing-Yi Ma^1,†, Xuelin Zhou^2,†, Jie Fu¹, Chi-Yu He¹, Ru Feng¹, Min Huang¹, Jia-Wen Shou¹

, Zhen-Xiong Zhao¹, Xiao-Yang Li¹, Luye Zhang¹, Yang-Chao Chen² and Yan Wang^1,*

¹ State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China

² School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Molecules 2016, 21(9), 1110; https://doi.org/10.3390/molecules21091110 - 24 Aug 2016

Cited by 16 | Viewed by 6097

Abstract

Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to [...] Read more.

Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MSⁿ-IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono-methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

▼ Show Figures

Figure 1

8 pages, 1177 KiB

Open AccessArticle

Ball Milling Assisted Solvent and Catalyst Free Synthesis of Benzimidazoles and Their Derivatives

by Taghreed H. EL-Sayed^1,2, Asmaa Aboelnaga^1,2 and Mohamed Hagar^1,3,*

¹ Faculty of Science, Chemistry Department, Yanbu, Taibah University, Yanbu, Saudi Arabia

² Faculty of Women for Arts, Science and Education, Chemistry Department, Ain Shams University, Heliopolis, Cairo 11757, Egypt

³ Faculty of Science, Chemistry Department, Alexandria University, Alexandria 21321, Egypt

Molecules 2016, 21(9), 1111; https://doi.org/10.3390/molecules21091111 - 24 Aug 2016

Cited by 28 | Viewed by 8212

Abstract

Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent-free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20 [...] Read more.

Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent-free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20 Hz frequency for one hour milling time. The study was extended for synthesis of a series of benzimidazol-2-one or benzimidazol-2-thione using different aldehydes; carboxylic acids; urea; thiourea or ammonium thiocyanate with o-phenylenediamine. Moreover; the alkylation of benzimidazolone or benzimidazolthione using ethyl chloroacetate was also studied. Full article

(This article belongs to the Special Issue Mechanochemistry)

▼ Show Figures

Graphical abstract

10 pages, 797 KiB

Open AccessCommunication

Three New Isoprenylated Flavonoids from the Root Bark of Morus alba

by Jae-Woo Jung¹, Ji-Hae Park¹, Yeong-Geun Lee¹

, Kyeong-Hwa Seo², Eun-Ji Oh¹, Dae-Young Lee³

, Dong-Wook Lim⁴, Daeseok Han⁴ and Nam-In Baek^1,*

¹ Graduate School of Biotechnology and Oriental Medicine Biotechnology, Kyung Hee University, Yongin 17104, Korea

² Natural Medicine Research Center, KRIBB, Chengju 28116, Korea

³ Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea

⁴ Division of Metabolism and Functionality Research, Korea Food Research Institute, Sungnam 463-746, Korea

Molecules 2016, 21(9), 1112; https://doi.org/10.3390/molecules21091112 - 24 Aug 2016

Cited by 25 | Viewed by 7229

Abstract

Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated [...] Read more.

Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated flavonoids: euchrenone a₇ (4), sanggenon J (5), kuwanon E (6), and kuwanon S (7). All compounds were isolated by repeated silica gel (SiO₂), octadecyl SiO₂ (ODS), and Sephadex LH-20 open column chromatography. The structure of the compounds were determined based on spectroscopic analyses, including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), and infrared (IR). In addition, compounds 1–4 were isolated for the first time from the root bark of M. alba in this study. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

▼ Show Figures

Figure 1

15 pages, 1465 KiB

Open AccessArticle

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

by Wen Ren^1,†, Qian Zhao^2,†, Chuan Zheng², Qiong Zhao², Li Guo^1,* and Wei Huang^2,*

¹ Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

² State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

Molecules 2016, 21(9), 1113; https://doi.org/10.3390/molecules21091113 - 24 Aug 2016

Cited by 6 | Viewed by 7791

Abstract

Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also [...] Read more.

Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures. Full article

(This article belongs to the Special Issue Pericyclic Reactions)

▼ Show Figures

Figure 1

11 pages, 2034 KiB

Open AccessArticle

Identification of a New Morpholine Scaffold as a P2Y12 Receptor Antagonist

by Young Ha Ahn^1,†, Joo-Youn Lee^1,2,†, Hee Dong Park³

, Tae Hun Kim³, Min Chul Park^4,5, Gildon Choi⁶ and Sunghoon Kim^1,4,*

¹ College of Pharmacy, Seoul National University, Seoul 08826, Korea

² Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea

³ LG Life Sciences Ltd., R & D Park, Daejeon 305-343, Korea

⁴ Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Korea

⁵ Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Korea

⁶ Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea

Molecules 2016, 21(9), 1114; https://doi.org/10.3390/molecules21091114 - 24 Aug 2016

Cited by 17 | Viewed by 5658

Abstract

The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For [...] Read more.

The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For this reason, ticagrelor—a new chemical class of P2Y12 receptor antagonist—was developed, but it can cause shortness of breath and various types of bleeding. Moreover, ticagrelor is a cytochrome P450 3A4 substrate/inhibitor and, therefore, caution should be exercised when it is used concomitantly with strong CYP3A4 inducers/inhibitors. There is a need for novel P2Y12 receptor antagonist scaffolds that are reversible and have high efficacy without associated side effects. Here, we describe a novel antagonist containing a morpholine moiety that was identified by screening libraries of commercially available compounds. The molecule, Compound E, acted on P2Y12, but not P2Y1 and P2Y13, and exhibited pharmacological characteristics that were distinct from those of ticagrelor, acting instead on P2Y12 via an allosteric mechanism. These results provide a basis for the development/optimization of a new class of P2Y12 antagonists. Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Figure 1

11 pages, 2700 KiB

Open AccessArticle

Ionic Liquids as Solvents for Rhodium and Platinum Catalysts Used in Hydrosilylation Reaction

by Witold Zielinski¹, Rafal Kukawka^1,2

, Hieronim Maciejewski^1,2 and Marcin Smiglak^1,2,*

¹ Poznan Science and Technology Park, Adam Mickiewicz University Foundation, 46 Rubież ST., 61-612 Poznań, Poland

² Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland

Molecules 2016, 21(9), 1115; https://doi.org/10.3390/molecules21091115 - 24 Aug 2016

Cited by 29 | Viewed by 7107 | Correction

Abstract

A group of imidazolium and pyridinium based ionic liquids has been synthetized, and their ability to dissolve and activate the catalysts used in hydrosilylation reaction of 1-octane and 1,1,1,3,5,5,5-heptamethyltrisiloxane was investigated. An organometallic catalyst as well as inorganic complexes of platinum and rhodium [...] Read more.

A group of imidazolium and pyridinium based ionic liquids has been synthetized, and their ability to dissolve and activate the catalysts used in hydrosilylation reaction of 1-octane and 1,1,1,3,5,5,5-heptamethyltrisiloxane was investigated. An organometallic catalyst as well as inorganic complexes of platinum and rhodium dissolved in ionic liquids were used, forming liquid solutions not miscible with the substrates or with the products of the reaction. The results show that application of such a simple biphasic catalytic system enables reuse of ionic liquid phase with catalysts in multiple reaction cycles reducing the costs and decreasing the amount of catalyst needed per mole of product. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

▼ Show Figures

Graphical abstract

9 pages, 534 KiB

Open AccessArticle

Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

by Lamiaa A. Shaala^1,2

, Diaa T. A. Youssef^3,*

, Jihan M. Badr^3,4 and Steve M. Harakeh⁵

¹ Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia

² Suez Canal University Hospital, Suez Canal University, Ismailia 41522, Egypt

³ Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

⁴ Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt

⁵ Special Infectious Agents Unit, Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Molecules 2016, 21(9), 1116; https://doi.org/10.3390/molecules21091116 - 24 Aug 2016

Cited by 38 | Viewed by 6326

Abstract

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H [...] Read more.

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC₅₀ of 1.5 μg/mL, while 1–10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Figure 1

10 pages, 3744 KiB

Open AccessArticle

Truncation Derivatives of the S-Layer Protein of Sporosarcina ureae ATCC 13881 (SslA): Towards Elucidation of the Protein Domain Responsible for Self-Assembly

by Melinda Varga

Electronics Packaging Laboratory, Department of Electrical Engineering and Information Technology, Technische Universität Dresden, 01069 Dresden, Germany

Molecules 2016, 21(9), 1117; https://doi.org/10.3390/molecules21091117 - 24 Aug 2016

Cited by 1 | Viewed by 7824

Abstract

The cell surface of Sporosarcina ureae ATCC 13881 is covered by an S-layer (SslA) consisting of identical protein subunits that assemble into lattices exhibiting square symmetry. In this work the self-assembly properties of the recombinant SslA were characterised with an emphasis on the [...] Read more.

The cell surface of Sporosarcina ureae ATCC 13881 is covered by an S-layer (SslA) consisting of identical protein subunits that assemble into lattices exhibiting square symmetry. In this work the self-assembly properties of the recombinant SslA were characterised with an emphasis on the identification of protein regions responsible for self-assembly. To this end, recombinant mature SslA (aa 31-1097) and three SslA truncation derivatives (one N-terminal, one C-terminal and one CN-terminal) were produced in a heterologous expression system, isolated, purified and their properties analysed by in vitro recrystallisation experiments on a functionalised silicon wafer. As a result, recombinant mature SslA self-assembled into crystalline monolayers with lattices resembling the one of the wild-type SslA. The study identifies the central protein domain consisting of amino acids 341-925 self-sufficient for self-assembly. Neither the first 341 amino acids nor the last 172 amino acids of the protein sequence are required to self-assemble into lattices. Full article

(This article belongs to the Special Issue Nanobiostructures: Commemorative Issue in Honor of Professor Serban Solacolu (1905-1980) - Founder of the Romanian School of Oxide Materials Science and Engineering)

▼ Show Figures

Figure 1

9 pages, 2615 KiB

Open AccessArticle

Adaptive Responses to Oxidative Stress in the Filamentous Fungal Shiraia bambusicola

by Huaxiang Deng, Jiajun Chen, Ruijie Gao, Xiangru Liao^* and Yujie Cai^*

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, China

Molecules 2016, 21(9), 1118; https://doi.org/10.3390/molecules21091118 - 24 Aug 2016

Cited by 30 | Viewed by 6685

Abstract

Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168 [...] Read more.

Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168 when treated with high concentrations of H₂O₂. Hypocrellin production was improved by nearly 27% and 25% after 72 h incubation with 10 mM and 20 mM H₂O₂, respectively, while the inhibition ratios of exogenous 20 mM H₂O₂ on wild S. bambusicola and a hypocrellin-deficient strain were 20% and 33%, respectively. Under exogenous oxidative stress, the specific activities of catalase, glutathione reductase, and superoxide dismutase were significantly increased. These changes may allow Shiraia to maintain normal life activities under oxidative stress. Moreover, sufficient glutathione peroxidase was produced in the SUPER-H168 and hypocrellin-deficient strains, to further ensure that S. bambusicola has excellent protective abilities against oxidative stress. This study creates the possibility that the addition of high H₂O₂ concentrations can stimulate fungal secondary metabolism, and will lead to a comprehensive and coherent understanding of mechanisms against oxidative stresses from high hydrogen peroxide concentrations in the filamentous fungal Shiraia sp. SUPER-H168. Full article

(This article belongs to the Special Issue Biosynthesis of Natural Products)

▼ Show Figures

Figure 1

10 pages, 1036 KiB

Open AccessArticle

Quantification of Oxidized and Unsaturated Bile Alcohols in Sea Lamprey Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry

by Ke Li, Anne M. Scott, Yu-Wen Chung-Davidson, Ugo Bussy, Trinkal Patel, Zoe E. Middleton and Weiming Li^*

Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI 48824, USA

Molecules 2016, 21(9), 1119; https://doi.org/10.3390/molecules21091119 - 24 Aug 2016

Cited by 2 | Viewed by 5510

Abstract

A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted [...] Read more.

A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted by n-hexane. Gradient UHPLC separation was performed using an Acquity BEH C18 column with a mobile phase of water and methanol containing 20 mM triethylamine. Multiple reaction monitoring modes of precursor-product ion transitions for each analyte was used. This method displayed good linearity, with correlation coefficients greater than 0.99, and was validated. Precision and accuracy (RSD %) were in the range of 0.31%–5.28%, while mean recoveries were between 84.3%–96.3%. With this technique, sea lamprey tissue samples were analyzed for unsaturated bile alcohol analytes. This method is practical and particularly suitable for widespread putative pheromone residue analysis. Full article

▼ Show Figures

Figure 1

15 pages, 741 KiB

Open AccessArticle

Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry

by Rodrigo P. Feliciano, Geoffrey Istas, Christian Heiss

and Ana Rodriguez-Mateos^*

Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, 40225 Düsseldorf, Germany

Molecules 2016, 21(9), 1120; https://doi.org/10.3390/molecules21091120 - 25 Aug 2016

Cited by 62 | Viewed by 9525

Abstract

Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual [...] Read more.

Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%–48% in plasma and 47%–54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

▼ Show Figures

Figure 1

11 pages, 1329 KiB

Open AccessArticle

Three Novel Triterpenoids from Taraxacum officinale Roots

by Takashi Kikuchi, Ayaka Tanaka, Mayu Uriuda, Takeshi Yamada

and Reiko Tanaka^*

Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Molecules 2016, 21(9), 1121; https://doi.org/10.3390/molecules21091121 - 27 Aug 2016

Cited by 20 | Viewed by 7014

Abstract

Three novel lupane-, bauerane-, and euphane-type triterpenoids (1–3), in addition to seven known triterpenoids (4–10)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8 [...] Read more.

Three novel lupane-, bauerane-, and euphane-type triterpenoids (1–3), in addition to seven known triterpenoids (4–10)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8), eupha-7,24-dien-3-one (9), and 24-oxoeupha-7,24-dien-3β-yl acetate (10)—were isolated from the roots of Taraxacum officinale. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D-NMR spectra and electron ionization mass spectrometry (EIMS). The effects of compounds 1–10 on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages were evaluated. Compounds 4, 6, and 10 exhibited similar NO inhibitory activities to N^G-monomethyl-l-arginine acetate (l-NMMA). These compounds did not exhibit cytotoxicity at an effective concentration. The results of present study suggest that compounds 4, 6, and 10 have potential as anti-inflammatory disease agents. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

▼ Show Figures

Figure 1

9 pages, 1434 KiB

Open AccessArticle

Keratin Protein-Catalyzed Nitroaldol (Henry) Reaction and Comparison with Other Biopolymers

by Marleen Häring^1,2, Asja Pettignano^1,2, Françoise Quignard², Nathalie Tanchoux²

and David Díaz Díaz^1,3,*

¹ Institute of Organic Chemistry, University of Regensburg, Universitätsstr 31, Regensburg 93053, Germany

² Institute Charles Gerhardt Montpellier-UMR 5253 CNRS/UM/ENSCM, Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'École Normale, Cedex 5, Montpellier 34296, France

³ IQAC-CSIC, Jordi Girona 18–26, Barcelona 08034, Spain

Molecules 2016, 21(9), 1122; https://doi.org/10.3390/molecules21091122 - 25 Aug 2016

Cited by 13 | Viewed by 6319

Abstract

Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry) reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO [...] Read more.

Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry) reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO and in water in the presence of tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. Negligible background reactions (i.e., negative control experiment in the absence of keratin protein) were observed in these solvent systems. Aromatic aldehydes bearing electron-donating groups and aliphatic aldehydes showed poor or no conversion, respectively. In general, the reactions in water/TBAB required twice the amount of time than in DMSO to achieve similar conversions. Moreover, comparison of the kinetics of the keratin-mediated nitroaldol (Henry) reaction with other biopolymers revealed slower rates for the former and the possibility of fine-tuning the kinetics by appropriate selection of the biopolymer and solvent. Full article

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

▼ Show Figures

Graphical abstract

13 pages, 1466 KiB

Open AccessArticle

Betulin Phosphonates; Synthesis, Structure, and Cytotoxic Activity

by Elwira Chrobak^1,*, Ewa Bębenek¹

, Monika Kadela-Tomanek¹, Małgorzata Latocha², Christian Jelsch³, Emmanuel Wenger³ and Stanisław Boryczka¹

¹ Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland

² Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 8 Jedności Str., 41-200 Sosnowiec, Poland

³ Laboratoire Cristallographie Résonance Magnétique et Modélisations, Faculté des Sciences et Technologies, CNRS, Université de Lorraine, BP 70239, 54506 Vandoeuvre-les-Nancy, France

Molecules 2016, 21(9), 1123; https://doi.org/10.3390/molecules21091123 - 26 Aug 2016

Cited by 29 | Viewed by 7337

Abstract

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification [...] Read more.

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification of products as E and Z isomers has been carried out using ¹H-, ¹³C-, ³¹P-NMR, and crystallographic analysis. The crystal structure in the orthorhombic space group and analysis of crystal packing contacts for 29-diethoxyphosphoryl-28-cyclopropylpropynoyloxy-lup-20E(29)-en-3β-ol 8a are reported. All new compounds were tested in vitro for their antiproliferative activity against human T47D (breast cancer), SNB-19 (glioblastoma), and C32 (melanoma) cell lines. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

▼ Show Figures

Graphical abstract

10 pages, 1458 KiB

Open AccessArticle

Evaluation of the Effect of Two Volatile Organic Compounds on Barley Pathogens

by Amine Kaddes¹, Olivier Parisi¹, Chadi Berhal¹, Sofiene Ben Kaab¹, Marie-Laure Fauconnier², Bouzid Nasraoui³, M. Haissam Jijakli¹, Sébastien Massart¹ and Caroline De Clerck^1,*

¹ Integrated and Urban Plant Pathology Laboratory, Gembloux Agro-Bio Tech (GxABT), University of Liège, Passage des Déportés 2, Gembloux 5030, Belgium

² General and Organic Chemistry Unit, Gembloux Agro-Bio Tech (GxABT), University of Liège, Passage des Déportés 2, Gembloux 5030, Belgium

³ Laboratory of Phytopathology, National Agronomic Institute of Tunisia, University of Carthage, Tunis 1082, Tunisia

Molecules 2016, 21(9), 1124; https://doi.org/10.3390/molecules21091124 - 26 Aug 2016

Cited by 9 | Viewed by 6048

Abstract

This study aimed to determine the effect of Volatile Organic Compounds (VOCs) on some pathogens, these VOCs were emitted during interactions of barley with Fusarium culmorum Schltdl and/or Cochliobolus sativus Shoemaker, two common root rot pathogens. Our work shows that two organic esters: [...] Read more.

This study aimed to determine the effect of Volatile Organic Compounds (VOCs) on some pathogens, these VOCs were emitted during interactions of barley with Fusarium culmorum Schltdl and/or Cochliobolus sativus Shoemaker, two common root rot pathogens. Our work shows that two organic esters: methyl propanoate (MP) and methyl prop-2-enoate (MA) significantly reduced the development of fungi in vitro. Additional tests showed that the esters significantly inhibited spore germination of these pathogens. The activity of these VOCs on a wide range of fungal and bacterial pathogens was also tested in vitro and showed inhibitory action. The effect of the VOCs on infected barley seeds also showed plantlets growing without disease symptoms. MA and MP seem to have potential value as alternative plant protection compounds against barley bioagressors. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

6 pages, 1040 KiB

Open AccessArticle

Cytotoxicity of Triterpenoid Alkaloids from Buxus microphylla against Human Tumor Cell Lines

by Shi-Tou Bai^1,2, Guo-Lei Zhu¹, Xing-Rong Peng^1,3, Jin-Run Dong^1,3, Mu-Yuan Yu¹, Jian-Chao Chen^1,2,3, Luo-Sheng Wan^1,3,* and Ming-Hua Qiu^1,2,3,*

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

² School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

³ Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

Molecules 2016, 21(9), 1125; https://doi.org/10.3390/molecules21091125 - 26 Aug 2016

Cited by 13 | Viewed by 5885

Abstract

Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (1–3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1–3 belong to [...] Read more.

Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (1–3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1–3 belong to the 9,10-cycloartane type alkaloids. In addition, compound 3 exhibited moderate cytotoxic activities in vitro against HL-60, SMMC-7221, A-549, MCF-7, and SW480 cell lines (with IC₅₀ values ranging from 4.51 to 15.58 μM). Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

▼ Show Figures

Figure 1

9 pages, 1128 KiB

Open AccessArticle

Aspirination of α-Aminoalcohol (Sarpogrelate M1)

by Sunhwa Park, Jiyun Lee, Kye Jung Shin and Jae Hong Seo^*

Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do 420-743, Korea

Molecules 2016, 21(9), 1126; https://doi.org/10.3390/molecules21091126 - 25 Aug 2016

Cited by 1 | Viewed by 6322

Abstract

Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary [...] Read more.

Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary α-amino group. After systematic analysis of those methods, the aspirinated sarpogrelate M1 was prepared using a two-step approach combining salicylate ester formation and acetylation. Full article

(This article belongs to the Section Organic Chemistry)

▼ Show Figures

Graphical abstract

14 pages, 10300 KiB

Open AccessArticle

Effects of (Oxy-)Fluorination on Various High-Performance Yarns

by Iris Kruppke^*,†

, Matthias Bartusch^†

, Rico Hickmann, Rolf-Dieter Hund and Chokri Cherif

Institute of Textile Machinery and High Performance Material Technology, Technische Universität Dresden, Hohe Straße 6, 01062 Dresden, Germany

Molecules 2016, 21(9), 1127; https://doi.org/10.3390/molecules21091127 - 26 Aug 2016

Cited by 8 | Viewed by 5893

Abstract

In this work, typical high-performance yarns are oxy-fluorinated, such as carbon fibers, ultra-high-molecular-weight polyethylene, poly(p-phenylene sulfide) and poly(p-phenylene terephthalamide). The focus is on the property changes of the fiber surface, especially the wetting behavior, structure and chemical composition. Therefore, [...] Read more.

In this work, typical high-performance yarns are oxy-fluorinated, such as carbon fibers, ultra-high-molecular-weight polyethylene, poly(p-phenylene sulfide) and poly(p-phenylene terephthalamide). The focus is on the property changes of the fiber surface, especially the wetting behavior, structure and chemical composition. Therefore, contact angle, XPS and tensile strength measurements are performed on treated and untreated fibers, while SEM is utilized to evaluate the surface structure. Different results for the fiber materials are observed. While polyethylene exhibits a relevant impact on both surface and bulk properties, polyphenylene terephthalamide and polyphenylene sulfide are only affected slightly by (oxy-)fluorination. The wetting of carbon fiber needs higher treatment intensities, but in contrast to the organic fibers, even its textile-physical properties are enhanced by the treatment. Based on these findings, the capability of (oxy-)fluorination to improve the adhesion of textiles in fiber-reinforced composite materials can be derived. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

▼ Show Figures

Graphical abstract

21 pages, 4296 KiB

Open AccessReview

Cardiac Meets Skeletal: What’s New in Microfluidic Models for Muscle Tissue Engineering

by Roberta Visone^1,†, Mara Gilardi^2,3,†, Anna Marsano⁴, Marco Rasponi¹, Simone Bersini^2,*,‡

and Matteo Moretti^{2,5,6,7,*,‡}

¹ Department of Electronics, Information and Bioengineering, Politecnico Di Milano, Milano 20133, Italy

² Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, Milano 20161, Italy

³ Department of Biotechnology and Biosciences, PhD School in Life Sciences, University of Milano-Bicocca, Milano 20126, Italy

⁴ Departments of Surgery and Biomedicine, University Basel, University Hospital Basel, Basel 4065, Switzerland

⁵ Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale, Lugano 6900, Switzerland

⁶ Swiss Institute for Regenerative Medicine, Lugano 6900, Switzerland

⁷ Cardiocentro Ticino, Lugano 6900, Switzerland

Molecules 2016, 21(9), 1128; https://doi.org/10.3390/molecules21091128 - 26 Aug 2016

Cited by 45 | Viewed by 15110

Abstract

In the last few years microfluidics and microfabrication technique principles have been extensively exploited for biomedical applications. In this framework, organs-on-a-chip represent promising tools to reproduce key features of functional tissue units within microscale culture chambers. These systems offer the possibility to investigate [...] Read more.

In the last few years microfluidics and microfabrication technique principles have been extensively exploited for biomedical applications. In this framework, organs-on-a-chip represent promising tools to reproduce key features of functional tissue units within microscale culture chambers. These systems offer the possibility to investigate the effects of biochemical, mechanical, and electrical stimulations, which are usually applied to enhance the functionality of the engineered tissues. Since the functionality of muscle tissues relies on the 3D organization and on the perfect coupling between electrochemical stimulation and mechanical contraction, great efforts have been devoted to generate biomimetic skeletal and cardiac systems to allow high-throughput pathophysiological studies and drug screening. This review critically analyzes microfluidic platforms that were designed for skeletal and cardiac muscle tissue engineering. Our aim is to highlight which specific features of the engineered systems promoted a typical reorganization of the engineered construct and to discuss how promising design solutions exploited for skeletal muscle models could be applied to improve cardiac tissue models and vice versa. Full article

(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)

▼ Show Figures

Figure 1

11 pages, 1730 KiB

Open AccessArticle

Triterpenes for Well-Balanced Scar Formation in Superficial Wounds

by Stefan Kindler¹, Matthias Schuster¹, Christian Seebauer¹, Rico Rutkowski¹, Anna Hauschild¹, Fred Podmelle¹, Camilla Metelmann², Bibiana Metelmann², Charlotte Müller-Debus³, Hans-Robert Metelmann^1,*

and Isabella Metelmann¹

¹ Department of Oral and Maxillofacial Surgery/Plastic Surgery, Greifswald University Medicine, Ferdinand-Sauerbruch-Str. DZ 7, Greifswald 17475, Germany

² Department of Anesthesiology, Anesthesia, Intensive Care-, Emergency- and Pain Medicine, Greifswald University Medicine, Ferdinand-Sauerbruch-Str., Greifswald 17475, Germany

³ Department of Surgery, Greifswald University Medicine, Ferdinand-Sauerbruch-Str., Greifswald 17475, Germany

Molecules 2016, 21(9), 1129; https://doi.org/10.3390/molecules21091129 - 27 Aug 2016

Cited by 7 | Viewed by 12835

Abstract

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as [...] Read more.

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients’ point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

▼ Show Figures

Figure 1

9 pages, 1033 KiB

Open AccessArticle

Characterization of a New Flavone and Tyrosinase Inhibition Constituents from the Twigs of Morus alba L.

by Long Zhang¹, Guanjun Tao¹, Jie Chen^1,2 and Zong-Ping Zheng^1,*

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China

² Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi 214122, Jiangsu, China

Molecules 2016, 21(9), 1130; https://doi.org/10.3390/molecules21091130 - 2 Sep 2016

Cited by 61 | Viewed by 9328

Abstract

The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 2–17 were [...] Read more.

The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 2–17 were isolated from M. alba twigs and their structures were identified by interpretation of the corresponding ESI-MS and NMR spectral data. In the tyrosinase inhibitory test, the compounds steppogenin (IC₅₀ 0.98 ± 0.01 µM), 2,4,2′,4′-tetrahydroxychalcone (IC₅₀ 0.07 ± 0.02 µM), morachalcone A (IC₅₀ 0.08 ± 0.02 µM), oxyresveratrol (IC₅₀ 0.10 ± 0.01 µM), and moracin M (8.00 ± 0.22 µM) exhibited significant tyrosinase inhibition activities, much stronger than that of the positive control kojic acid. These results suggest that M. alba twig extract should served as a good source of natural tyrosinase inhibitors for use in foods as antibrowning agents or in cosmetics as skin-whitening agents. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Graphical abstract

14 pages, 1016 KiB

Open AccessArticle

New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07

by Olga N. Sekurova¹, Ignacio Pérez-Victoria²

, Jesús Martín², Kristin F. Degnes³, Håvard Sletta³, Fernando Reyes²

and Sergey B. Zotchev^1,*

¹ Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria

² Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Armilla, Granada, Spain

³ Department of Biotechnology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway

Molecules 2016, 21(9), 1131; https://doi.org/10.3390/molecules21091131 - 27 Aug 2016

Cited by 9 | Viewed by 7472

Abstract

Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine [...] Read more.

Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated. Biological activity tests of two of the new deferoxamine analogues revealed weak activity against Escherichia coli. The gene knockout experiment in the gene cluster targeted for activation, as well as overexpression of certain genes from this cluster did not have an effect on the production of these compounds by the strain overexpressing the regulator. It seems plausible that the production of such compounds is a response to stress imposed by the production of an as-yet unidentified metabolite specified by the cryptic cluster. Full article

(This article belongs to the Special Issue Genomics-based Discovery of Microbial Natural Products)

▼ Show Figures

Figure 1

13 pages, 906 KiB

Open AccessArticle

Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate

by Celia Bustos-Brito^1,*

, Valeria J. Vázquez-Heredia¹, Fernando Calzada², Lilian Yépez-Mulia³, José S. Calderón¹, Simón Hernández-Ortega¹, Baldomero Esquivel¹, Normand García-Hernández⁴

and Leovigildo Quijano^1,*

¹ Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, D.F. 04510, Mexico

² UIM en Farmacología, 2o Piso CORCE, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Av. Cuauhtémoc 330, Col. Doctores, México, D.F. 06725, Mexico

³ UIM en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Av. Cuauhtémoc 330, Col. Doctores, México, D.F. 06725, Mexico

⁴ UIM en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Centro Médico Nacional Siglo XXI, IMSS, Av. Cuauhtémoc 330, Col. Doctores, México, D.F. 06725, Mexico

Molecules 2016, 21(9), 1132; https://doi.org/10.3390/molecules21091132 - 12 Sep 2016

Cited by 13 | Viewed by 6361

Abstract

Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with [...] Read more.

Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3) were also obtained. In this paper, we report the structures and complete assignments of the ¹H and ¹³C-NMR data of compounds 1–7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

▼ Show Figures

Graphical abstract

11 pages, 1110 KiB

Open AccessArticle

Anti-Influenza Virus Activity and Constituents Characterization of Paeonia delavayi Extracts

by Jinhua Li, Xianying Yang and Linfang Huang^*

Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100193, China

Molecules 2016, 21(9), 1133; https://doi.org/10.3390/molecules21091133 - 26 Aug 2016

Cited by 28 | Viewed by 5610

Abstract

Paeonia delavayi, an endemic species in southwestern China, has been widely used as a traditional remedy for cardiovascular, extravasated blood, stagnated blood and female diseases in traditional Chinese medicine (TCM). However, there are no reports on the anti-influenza virus activity of this species. [...] Read more.

Paeonia delavayi, an endemic species in southwestern China, has been widely used as a traditional remedy for cardiovascular, extravasated blood, stagnated blood and female diseases in traditional Chinese medicine (TCM). However, there are no reports on the anti-influenza virus activity of this species. Here, the anti-influenza virus activity of P. delavayi root extracts was first evaluated by an influenza virus neuraminidase (NA) inhibition assay. Meantime, constituents in the active extracts were identified using ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and seven major identified constituents were used to further evaluate the NA inhibitory activity. The results showed that the ethyl acetate fraction (EA) and the ethanol fraction (E) of P. delavayi both presented strong NA inhibitory activity with IC₅₀ values of 75.932 μg/mL and 83.550 μg/mL, respectively. Twenty-seven constituents were characterized in these two active extracts by UPLC-Q-TOF-MS analysis, and seven major identified constituents exhibited high activity against the influenza virus. Among them, Benzoylpaeoniflorin (IC₅₀ = 143.701 µM) and pentagalloylglucose (IC₅₀ = 62.671 µM) exhibited the highest activity against the influenza virus, even far stronger than oseltamivir acid (IC₅₀ = 281.308 µM). This study indicated that P. delavayi was a strong NA inhibitor, but cell-based inhibition, anti-influenza virus activity in vivo and anti-influenza virus mechanism still need to be tested and explored. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

11 pages, 6998 KiB

Open AccessArticle

Construction and Quality Analysis of Transgenic Rehmannia glutinosa Containing TMV and CMV Coat Protein

by Zhongqiu Teng^1,2,3,†, Ye Shen^1,†, Jing Li¹, Zhongping Lin⁴, Min Chen¹, Min Wang¹, Man Li¹, Hongran Dong¹ and Luqi Huang^1,*

¹ State Key Laboratory Breeding Base of Dao-Di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

² State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

³ Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China

⁴ National Key Laboratory of Protein Engineering and Plant Genetic Engineering, College of life science, Peking University, Beijing 100871, China

Molecules 2016, 21(9), 1134; https://doi.org/10.3390/molecules21091134 - 27 Aug 2016

Cited by 7 | Viewed by 5865

Abstract

Plant viruses, especially tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) are serious threats to Rehmannia glutinosa which is a “top grade” herb in China. In the present study, TMV- and CMV-resistant Rehmannia glutinosa Libosch. plants were constructed by transforming the protein [...] Read more.

Plant viruses, especially tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) are serious threats to Rehmannia glutinosa which is a “top grade” herb in China. In the present study, TMV- and CMV-resistant Rehmannia glutinosa Libosch. plants were constructed by transforming the protein (CP) genes of TMV and CMV into Rehmannia glutinosa via a modified procedure of Agrobacterium tumefaciens-mediated transformation. Integration and expression of TMV CP and CMV CP transgenes in 2 lines, LBA-1 and LBA-2, were confirmed by PCR, Southern blot and RT-PCR. Both LBA-1 and LBA-2 were resistant to infection of homologous TMV and CMV strains. The quality of transgenic Rehmanniae Radix was evaluated based on fingerprint analysis and components quantitative analysis comparing with control root tubes. These results showed that chemical composition of transgenic Rehmanniae Radix were similar to non-transgenic ones, which demonstrated that the medical quality and biosafety of transgenic Rehmanniae Radix were equivalent to non-transgenic material when consumed as traditional Chinese medicinal (TCM). Full article

▼ Show Figures

Figure 1

12 pages, 1483 KiB

Open AccessArticle

Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

by Yo-Han Han^1,†, Ji-Ye Kee^1,2,†, Dae-Seung Kim¹, Jeong-geon Mun¹, Mi-Young Jeong², Sang-Hyun Park³, Byung-Min Choi⁴, Sung-Joo Park⁵, Hyun-Jung Kim⁶, Jae-Young Um^7,* and Seung-Heon Hong^1,*

¹ Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea

² Center for Metabolic Function Regulation, Wonkwang University, Iksan, Jeonbuk 54538, Korea

³ Isotope Sciences Lab, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 54538, Korea

⁴ Department of Biochemistry, School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Korea

⁵ Department of Herbology, College of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Korea

⁶ Department of Herb Science, Dong-eui institute of technology, 54 Yangji-ro, Busanjin-gu, Busan 47230, Korea

⁷ Department of Pharmacology, College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea

Molecules 2016, 21(9), 1135; https://doi.org/10.3390/molecules21091135 - 27 Aug 2016

Cited by 38 | Viewed by 9841

Abstract

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a [...] Read more.

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Graphical abstract

12 pages, 2196 KiB

Open AccessReview

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents

by Chang-Ik Choi

College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea

Molecules 2016, 21(9), 1136; https://doi.org/10.3390/molecules21091136 - 27 Aug 2016

Cited by 97 | Viewed by 15520

Abstract

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight [...] Read more.

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

▼ Show Figures

Figure 1

11 pages, 2722 KiB

Open AccessArticle

The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction

by Hyun-Jin An¹, Jung-Yeon Kim¹, Woon-Hae Kim¹

, Sang-Mi Han² and Kwan-Kyu Park^1,*

¹ Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea

² Deparment of Agricultural Biology, National Academy of Agricultural Science, RDA, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju 54875, Korea

Molecules 2016, 21(9), 1137; https://doi.org/10.3390/molecules21091137 - 27 Aug 2016

Cited by 25 | Viewed by 8758

Abstract

Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study [...] Read more.

Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-β1 (TGF-β1). Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic genes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also effectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings suggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic agent for the prevention of fibrosis that characterizes the progression of chronic kidney disease. Full article

▼ Show Figures

Figure 1

8 pages, 2243 KiB

Open AccessArticle

Screening for Neuraminidase Inhibitory Activity in Traditional Chinese Medicines Used to Treat Influenza

by Xian-Ying Yang^1,2, Ai-lin Liu³, Shu-jing Liu⁴, Xiao-wei Xu⁴ and Lin-Fang Huang^1,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² College of Pharmacy and Chemistry, Dali University, Yunnan 671000, China

³ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Molecules 2016, 21(9), 1138; https://doi.org/10.3390/molecules21091138 - 27 Aug 2016

Cited by 23 | Viewed by 7878

Abstract

Objective: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from [...] Read more.

Objective: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from 113 TCM. The medicine extracts were then reacted with oseltamivir, using 2’-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as the substrate, to determine influenza virus neuraminidase activity using a standard fluorimetric assay. It was found that Chinese medicine extracts from Pyrola calliantha, Cynanchum wilfordii, Balanophora involucrata and Paeonia delavayi significantly inhibited neuraminidase activity at a concentration of 40 μg/mL. Dose-dependent inhibitory assays also revealed significant inhibition. The IC₅₀ range of the TCM extracts for influenza virus neuraminidase was approximately 12.66–34.85 μg/mL, respectively. Some Chinese medicines have clear anti-influenza viral effects that may play an important role in the treatment of influenza through the inhibition of viral neuraminidase. The results of this study demonstrated that plant medicines can serve as a useful source of neuraminidase (NA) inhibitors and further investigation into the pharmacologic activities of these extracts is warranted. Full article

▼ Show Figures

Figure 1

12 pages, 1384 KiB

Open AccessArticle

Structural Modifications of Deoxycholic Acid to Obtain Three Known Brassinosteroid Analogues and Full NMR Spectroscopic Characterization

by Heidy Herrera¹, Rodrigo Carvajal¹, Andrés F. Olea² and Luis Espinoza^1,*

¹ Departamento de Química, Universidad Técnica Federico Santa María, Av. España No. 1680, Valparaíso 2340000, Chile

² Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Santiago 8910339, Chile

Molecules 2016, 21(9), 1139; https://doi.org/10.3390/molecules21091139 - 27 Aug 2016

Cited by 7 | Viewed by 7225

Abstract

An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure, [...] Read more.

An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure, the di-oxidized product 6, obtained in the oxidation of methyl hyodeoxycholate 5, was converted almost quantitatively into the target monoketone 7 by stereoselective reduction with NaBH₄, increasing the overall yield of this synthetic route to 96.8%. The complete ¹H- and ¹³C-NMR assignments for all compounds synthesized in this work have been made by 1D and 2D heteronuclear correlation gs-HSQC and gs-HMBC techniques. Thus, it was possible to update the spectroscopic information of ¹H-NMR and to accomplish a complete assignment of all ¹³C-NMR signals for analogues 5–16, which were previously reported only in partial form. Full article

(This article belongs to the Section Organic Chemistry)

▼ Show Figures

Figure 1

14 pages, 1279 KiB

Open AccessArticle

Practical and Efficient Synthesis of α-Aminophosphonic Acids Containing 1,2,3,4-Tetrahydroquinoline or 1,2,3,4-Tetrahydroisoquinoline Heterocycles

by Mario Ordóñez^1,*

, Alicia Arizpe², Fracisco J. Sayago², Ana I. Jiménez² and Carlos Cativiela^2,*

¹ Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, Morelos, Mexico

² Departamento de Química Orgánica, Universidad de Zaragoza-CSIC, ISQCH, Zaragoza 50009, Spain

Molecules 2016, 21(9), 1140; https://doi.org/10.3390/molecules21091140 - 31 Aug 2016

Cited by 30 | Viewed by 8413

Abstract

We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in [...] Read more.

We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in the N-acyliminium ion intermediates, obtained from activation of the quinoline and isoquinoline heterocycles or from the appropriate δ-lactam with benzyl chloroformate. Finally, the hydrolysis of phosphonate moiety with simultaneous cleavage of the carbamate afforded the target compounds. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

▼ Show Figures

Figure 1

31 pages, 10942 KiB

Open AccessReview

Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives

by José Luis Viveros-Ceballos¹, Mario Ordóñez^2,*

, Francisco J. Sayago³ and Carlos Cativiela^3,*

¹ Secretaría Académica, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, 62209 Cuernavaca, Morelos, Mexico

² Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, 62209 Cuernavaca, Morelos, Mexico

³ Departamento de Química Orgánica, Universidad de Zaragoza-CSIC, ISQCH, 50009 Zaragoza, Spain

Molecules 2016, 21(9), 1141; https://doi.org/10.3390/molecules21091141 - 29 Aug 2016

Cited by 32 | Viewed by 9187

Abstract

α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic [...] Read more.

α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic processes, primarily acting as inhibitors for proteolytic enzymes where molecular stereochemistry has proven to be critical. This review summarizes the latest developments in the asymmetric synthesis of acyclic and phosphacyclic α-amino-C-phosphinic acids and derivatives, following in the first case an order according to the strategy used, whereas for cyclic compounds the nitrogen embedding in the heterocyclic core is considered. In addition selected examples of pharmacological implications of title compounds are also disclosed. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

▼ Show Figures

Graphical abstract

11 pages, 1018 KiB

Open AccessArticle

Arginine: New Insights into Growth Performance and Urinary Metabolomic Profiles of Rats

by Guangmang Liu^1,2,*, Xianjian Wu^1,2, Gang Jia^1,2, Xiaoling Chen^1,2, Hua Zhao^1,2, Jing Wang³, Caimei Wu^1,2 and Jingyi Cai^1,2

¹ Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, Sichuan, China

² Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu 611130, Sichuan, China

³ Maize Research Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China

Molecules 2016, 21(9), 1142; https://doi.org/10.3390/molecules21091142 - 29 Aug 2016

Cited by 9 | Viewed by 5107

Abstract

Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through ¹H-NMR spectroscopy. Twenty rats were randomly assigned to [...] Read more.

Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through ¹H-NMR spectroscopy. Twenty rats were randomly assigned to two groups supplemented with 0% or 1.0% l-arginine for 4 weeks. Urine samples were analyzed through NMR-based metabolomics. Arginine supplementation significantly increased the urine levels of 4-aminohippurate, acetate, creatine, creatinine, ethanolamine, formate, hippurate, homogentisate, indoxyl sulfate, and phenylacetyglycine. Conversely, arginine decreased the urine levels of acetamide, β-glucose, cirtulline, ethanol, glycine, isobutyrate, lactate, malonate, methymalonate, N-acetylglutamate, N-methylnicotinamide, and propionate. Results suggested that arginine can alter common systemic metabolic processes, including energy metabolism, amino acid metabolism, and gut microbiota metabolism. Moreover, the results also imply a possible physiological role of the metabolism in mediating the arginine supplementation-supported growth of rats. Full article

(This article belongs to the Section Metabolites)

▼ Show Figures

Figure 1

12 pages, 4777 KiB

Open AccessArticle

In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke

by Fang Zhang^†

, Xiaohui Duan^†, Liejing Lu, Xiang Zhang, Xiaomei Zhong, Jiaji Mao, Meiwei Chen and Jun Shen^*

Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China

Molecules 2016, 21(9), 1143; https://doi.org/10.3390/molecules21091143 - 29 Aug 2016

Cited by 20 | Viewed by 6650

Abstract

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs [...] Read more.

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs in stroke. Previously, we have successfully realized in vivo targeted MR imaging of endogenous NSCs in normal adult mice brains by using anti-CD15 antibody-conjugated superparamagnetic iron oxide nanoparticles (anti-CD15-SPIONs) as the molecular probe. Herein, we explore the performance of this molecular probe in targeted in vivo tracking of activated endogenous NSCs in ischemic stroke. Our study showed that intraventricular injection of anti-CD15-SPIONs could label activated endogenous NSCs in situ seven days after ischemic stroke, which were detected as enlarged areas of hypo-intense signals on MR imaging at 7.0 T. The treatment of cytosine arabinosine could inhibit the activation of endogenous NSCs, which was featured by the disappearance of areas of hypo-intense signals on MR imaging. Using anti-CD15-SPIONs as imaging probes, the dynamic process of activation of endogenous NSCs could be readily monitored by in vivo MR imaging. This targeted imaging strategy would be of great benefit to develop a new therapeutic strategy utilizing endogenous NSCs for ischemic stroke. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Graphical abstract

23 pages, 8745 KiB

Open AccessArticle

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

by Natascha Nebel, Simone Maschauer

, Torsten Kuwert, Carsten Hocke and Olaf Prante^*

Molecular Imaging and Radiochemistry, Department of Nuclear Medicine, Friedrich Alexander University (FAU), Erlangen 91054, Germany

Molecules 2016, 21(9), 1144; https://doi.org/10.3390/molecules21091144 - 29 Aug 2016

Cited by 14 | Viewed by 7458

Abstract

Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled [...] Read more.

Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. The three candidates [¹⁸F]1, [¹⁸F]2a and [¹⁸F]2b were chosen for in vitro and in vivo characterization as radioligands suitable for selective PET imaging of the D3 receptor. Their evaluation included the analysis of radiometabolites and the assessment of non-specific binding by in vitro rat brain autoradiography. While [¹⁸F]1 and [¹⁸F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4) with the candidate [¹⁸F]2b offering a B_max of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [¹⁸F]2a and [¹⁸F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Graphical abstract

11 pages, 2125 KiB

Open AccessArticle

Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

by Shifeng Wang¹, Chenxi Zhai¹, Yanling Zhang¹, Yangyang Yu¹, Yuxin Zhang¹, Lianghui Ma², Shiyou Li^3,* and Yanjiang Qiao^1,*

¹ Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing 100102, China

² HD Biosciences, Co., Ltd., 590 Ruiqing Road, Zhangjiang Hi-Tech Park East Campus, Pudong New Area, Shanghai 201201, China

³ Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China

Molecules 2016, 21(9), 1145; https://doi.org/10.3390/molecules21091145 - 29 Aug 2016

Cited by 24 | Viewed by 7738

Abstract

The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be [...] Read more.

The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC₅₀ of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

▼ Show Figures

Figure 1

8 pages, 685 KiB

Open AccessArticle

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii

by Dongsheng Fan, Guo-Yuan Zhu, Ting Li, Zhi-Hong Jiang^* and Li-Ping Bai^*

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China

Molecules 2016, 21(9), 1146; https://doi.org/10.3390/molecules21091146 - 29 Aug 2016

Cited by 16 | Viewed by 5463

Abstract

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well [...] Read more.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

18 pages, 3242 KiB

Open AccessArticle

Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases

by Nadia Calabriso¹, Marika Massaro¹

, Egeria Scoditti¹

, Mariangela Pellegrino^1,2, Ilaria Ingrosso³, Giovanna Giovinazzo³ and Maria Annunziata Carluccio^1,*

¹ National Research Council–Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy

² Department of Biological and Environmental Science and Technologies (DISTEBA), University of Salento, Lecce 73100, Italy

³ National Research Council–Institute of Science of Food Production, Lecce 73100, Italy

Molecules 2016, 21(9), 1147; https://doi.org/10.3390/molecules21091147 - 29 Aug 2016

Cited by 42 | Viewed by 8704

Abstract

Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to [...] Read more.

Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5–25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

▼ Show Figures

Graphical abstract

12 pages, 1807 KiB

Open AccessArticle

Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts and α-Glucosidase Inhibitory Activities of Different Fractionations

by Shuxia Yan^1,2, Xianan Zhang^1,2, Xin Wen^1,2, Qiang Lv^1,2, Changjie Xu^1,2, Chongde Sun^1,2 and Xian Li^1,2,*

¹ Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou 310058, China

² Laboratory of Fruit Quality Biology, the State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou 310058, China

Molecules 2016, 21(9), 1148; https://doi.org/10.3390/molecules21091148 - 31 Aug 2016

Cited by 30 | Viewed by 8737

Abstract

Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside [...] Read more.

Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak^® cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC₅₀ = 15.4–69.5 μg/mL), which were higher than that of positive control acarbose (IC₅₀ = 383.2 μg/mL). Four purified compounds 1–4 exerted α-glucosidase inhibitory activities, with IC₅₀ values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Graphical abstract

11 pages, 2152 KiB

Open AccessArticle

Panax Notoginseng Saponins as a Novel Nature Stabilizer for Poorly Soluble Drug Nanocrystals: A Case Study with Baicalein

by Yuanbiao Xie^1,†, Yueqin Ma^2,†, Junnan Xu¹, Yang Liu¹, Pengfei Yue^1,*, Qin Zheng¹, Pengyi Hu¹ and Ming Yang¹

¹ Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

² Department of Pharmaceutics, 94th Hospital of People’s Liberation Army, Nanchang 330000, China

Molecules 2016, 21(9), 1149; https://doi.org/10.3390/molecules21091149 - 30 Aug 2016

Cited by 21 | Viewed by 6085

Abstract

This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL [...] Read more.

This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL nanocrystals (BCL-NC) stabilized with panax notoginseng saponins (PNS). It was found that PNS was able to prevent the aggregation of BCL-NS during storage and improve the redispersibility of BCL-NC after freeze-drying and spray-drying, compared with polymer stabilizer PVPK30. The freeze-dried and spray-dried BCL-NC with PNS exhibited excellent performance as evidenced by scanning_electron_microscope (SEM) analysis. It was the reason that PNS possessed the interfacial property (41.69 ± 0.32 mN/m) and electrostatic effect (−40.1 ± 1.6 mV), which could easily adsorb onto the surface of hydrophobic BCL nanocrystals and prevent from its aggregation. It is concluded that PNS can be used as an effective nature stabilizer for production of drug nanocrystals. Full article

▼ Show Figures

Graphical abstract

10 pages, 940 KiB

Open AccessArticle

Chemical Composition, Antioxidant, and Antibacterial Activity of Wood Vinegar from Litchi chinensis

by Jyh-Ferng Yang¹, Cheng-Hong Yang², Ming-Tsai Liang¹, Zi-Jie Gao¹, Yuh-Wern Wu^1,* and Li-Yeh Chuang^1,*

¹ Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 840, Taiwan

² Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 807, Taiwan

Molecules 2016, 21(9), 1150; https://doi.org/10.3390/molecules21091150 - 30 Aug 2016

Cited by 152 | Viewed by 17674

Abstract

The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the [...] Read more.

The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the compositions in the wood vinegar. Three major components, included 2,6-dimethoxyphenol (syringol, 29.54%), 2-methoxyphenol (guaiacol, 12.36%), and 3,5-dimethoxy-4-hydroxytoluene (11.07%), were found in the wood vinegar. Antioxidant activities of the acids were investigated from the aspects of 1,1-Diphyl-2-picrylhydrazyl (DPPH) free radicals scavenging capacity, superoxide anion radical scavenging capacity, and reducing power. The pyroligneous acid exhibited high antioxidant activity which was comparable to the reference standards (vitamin C and butylated hydroxyl toluene) at the same dose with IC₅₀ values of 36.5 ppm calculated by the DPPH radical scavenging assay, 38.38 g Trolox equivalent/100 g DW by the trolox equivalent antioxidant capacity (TEAC) assay, and 67.9 by the reducing power analysis. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically antibiotic resistant isolates. The major components exhibited broad spectrum inhibition against all the bacterial strains with a range of disc inhibition zoon between 15–19 mm. The minimum inhibition concentration and minimum bactericide concentration against the test strains was ranging in 0.95–3.80 μL/100 μL and 1.90–3.80 μL/100 μL, respectively. Most of the antibiotic resistant strains were more susceptible to the wood vinegar than the non-antibiotic resistant strain except the strain of ornithine resistant Staphylococcus aureus. Based on the chemical profile, it was considered that the strongest antioxidant and antibacterial activity of Litchi chinensis wood vinegar was due to its highly phenolic compositions. This study revealed that the Litchi chinensis wood vinegar is valuable to develop as alternative food antioxidant and antibiotics. Full article

(This article belongs to the Collection Herbal Medicine Research)

▼ Show Figures

Figure 1

16 pages, 5155 KiB

Open AccessArticle

Photostabilizing Efficiency of Poly(vinyl chloride) in the Presence of Organotin(IV) Complexes as Photostabilizers

by Mustafa M. Ali¹, Gamal A. El-Hiti^2,*

and Emad Yousif^1,*

¹ Department of Chemistry, College of Science, Al-Nahrain University, Baghdad 64021, Iraq

² Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

Molecules 2016, 21(9), 1151; https://doi.org/10.3390/molecules21091151 - 30 Aug 2016

Cited by 56 | Viewed by 5757

Abstract

Three organotin complexes containing furosemide as a ligand (L), Ph₃SnL, Me₂SnL₂ and Bu₂SnL₂, were synthesized and characterized. Octahedral geometry was proposed for the Me₂SnL₂ and Bu₂SnL₂, while [...] Read more.

Three organotin complexes containing furosemide as a ligand (L), Ph₃SnL, Me₂SnL₂ and Bu₂SnL₂, were synthesized and characterized. Octahedral geometry was proposed for the Me₂SnL₂ and Bu₂SnL₂, while the Ph₃SnL complex has trigonal bipyramid geometry. The synthesized organotin complexes (0.5% by weight) were used as additives to improve the photostability of poly(vinyl chloride), PVC, (40 μm thickness) upon irradiation. The changes imposed on functional groups, weight loss and viscosity average molecular weight of PVC films were monitored. The experimental results show that the rate of photodegradation was reduced in the presence of the organotin additives. The quantum yield of the chain scission was found to be low (9.8 × 10⁻⁷) when Ph₃SnL was used as a PVC photostabilizer compared to controlled PVC (5.18 × 10⁻⁶). In addition, the atomic force microscope images for the PVC films containing Ph₃SnL₂ after irradiation shows a smooth surface compared to the controlled films. The rate of PVC photostabilization was found to be highest for Ph₃SnL followed by Bu₂SnL₂ and Me₂SnL₂. It has been suggested that the organotin complexes could act as hydrogen chloride scavengers, ultraviolet absorbers, peroxide decomposers and/or radical scavengers. Full article

▼ Show Figures

Graphical abstract

8 pages, 629 KiB

Open AccessArticle

Mexicanolide-Type Limonoids from the Roots of Trichilia sinensis

by Shou-Bai Liu^1,2, Wen-Li Mei², Hui-Qin Chen², Zhi-Kai Guo², Hao-Fu Dai^2,* and Zhu-Nian Wang^1,*

¹ Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou 571737, China

² Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China

Molecules 2016, 21(9), 1152; https://doi.org/10.3390/molecules21091152 - 30 Aug 2016

Cited by 11 | Viewed by 5020

Abstract

Four new mexicanolide-type limonoids 1–4, along with two known limonoids 5–6, were isolated from the ethanolic extracts of roots of the Traditional Chinese Medicine Trichilia sinensis. Their structures were unambiguously determined by analysis of spectroscopic data, [...] Read more.

Four new mexicanolide-type limonoids 1–4, along with two known limonoids 5–6, were isolated from the ethanolic extracts of roots of the Traditional Chinese Medicine Trichilia sinensis. Their structures were unambiguously determined by analysis of spectroscopic data, including 1D and 2D NMR as well as MS, and by comparison with literature data. In addition, the acetylcholinesterase (AChE) inhibitory activity of compounds 1–6 was evaluated by the Ellman method. All these compounds showed weak AChE inhibitory activity, with the inhibition percentages ranging from 18.5% to 27.8%. Full article

▼ Show Figures

Figure 1

9 pages, 861 KiB

Open AccessArticle

Passerini Reactions on Biocatalytically Derived Chiral Azetidines

by Lisa Moni¹

, Luca Banfi¹

, Andrea Basso¹, Andrea Bozzano¹, Martina Spallarossa¹, Ludger Wessjohann²

and Renata Riva^1,*

¹ Department of Chemistry and Industrial Chemistry, University of Genova, via Dodecaneso, 31-16146 Genova, Italy

² Leibniz-Institut für Pflanzenbiochemie, Weinberg 3, 06120 Halle (Saale), Germany

Molecules 2016, 21(9), 1153; https://doi.org/10.3390/molecules21091153 - 30 Aug 2016

Cited by 16 | Viewed by 5794

Abstract

The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity [...] Read more.

The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity was poor under classical Passerini conditions, a significant increase of diastereoselectivity (up to 76:24) was gained by the use of zinc bromide as promoter. The methodology has a broad scope and yields are always good. Full article

(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)

▼ Show Figures

Graphical abstract

8 pages, 357 KiB

Open AccessArticle

Development and Validation of a Kit to Measure Drink Antioxidant Capacity Using a Novel Colorimeter

by Alexandros Priftis¹, Dimitrios Stagos¹, Nikolaos Tzioumakis², Konstantinos Konstantinopoulos³, Anastasia Patouna⁴, Georgios E. Papadopoulos¹, Aristides Tsatsakis⁵ and Dimitrios Kouretas^1,*

¹ Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece

² Polytech S.A., Larissa 41222, Greece

³ Coffee Island S.A., Patras 26334, Greece

⁴ Department of Agricultural Engineering Technologists, TEI of Thessaly, Larissa 41110, Greece

⁵ Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece

Molecules 2016, 21(9), 1154; https://doi.org/10.3390/molecules21091154 - 30 Aug 2016

Cited by 1 | Viewed by 4483

Abstract

Measuring the antioxidant capacity of foods is essential, as a means of quality control to ensure that the final product reaching the consumer will be of high standards. Despite the already existing assays with which the antioxidant activity is estimated, new, faster and [...] Read more.

Measuring the antioxidant capacity of foods is essential, as a means of quality control to ensure that the final product reaching the consumer will be of high standards. Despite the already existing assays with which the antioxidant activity is estimated, new, faster and low cost methods are always sought. Therefore, we have developed a novel colorimeter and combined it with a slightly modified DPPH assay, thus creating a kit that can assess the antioxidant capacity of liquids (e.g., different types of coffee, beer, wine, juices) in a quite fast and low cost manner. The accuracy of the colorimeter was ensured by comparing it to a fully validated Hitachi U-1900 spectrophotometer, and a coefficient was calculated to eliminate the observed differences. In addition, a new, user friendly software was developed, in order to render the procedure as easy as possible, while allowing a central monitoring of the obtained results. Overall, a novel kit was developed, with which the antioxidant activity of liquids can be measured, firstly to ensure their quality and secondly to assess the amount of antioxidants consumed with the respective food. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

13 pages, 2665 KiB

Open AccessArticle

Facile Access to Stable Silylium Ions Stabilized by N-Heterocyclic Imines

by Tatsumi Ochiai¹, Tibor Szilvási² and Shigeyoshi Inoue^1,3,*

¹ Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 135, Sekr. C2, 10623 Berlin, Germany

² Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szent Gellért tér 4, 1111 Budapest, Hungary

³ Department of Chemistry, Catalysis Research Center and Institute of Silicon Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany

Molecules 2016, 21(9), 1155; https://doi.org/10.3390/molecules21091155 - 30 Aug 2016

Cited by 12 | Viewed by 8399

Abstract

Novel silylium ions with N-heterocyclic imines were successfully synthesized. The reaction of trimethylsilyl imidazolin-2-imine Me₃SiNIPr (NIPr = bis(2,6-diisopropylphenyl)-imidazolin-2-imino) with B(C₆F₅)₃ leads to dimeric imino-substituted silylium ions through a methyl group abstraction on the silicon atom. [...] Read more.

Novel silylium ions with N-heterocyclic imines were successfully synthesized. The reaction of trimethylsilyl imidazolin-2-imine Me₃SiNIPr (NIPr = bis(2,6-diisopropylphenyl)-imidazolin-2-imino) with B(C₆F₅)₃ leads to dimeric imino-substituted silylium ions through a methyl group abstraction on the silicon atom. Meanwhile, the intermolecular imino-coordinated silylium ion is formed by using the less sterically crowded imine Me₃SiNItBu (NItBu = bis(tert-butyl)-imidazolin-2-imino). Furthermore, the treatment of dimethylchlorosilane Me₂(Cl)SiNIPr with AgOTf affords the contact ion pair Me₂(OTf)SiNIPr by substitution of the chloride. A novel complex with the formula [Me₂(DMAP)SiNIPr][OTf] was prepared by coordination with 4-dimethylamino-pyridine (DMAP). In the solid state, the DMAP adduct [Me₂(DMAP)SiNIPr][OTf] contains a distinct [Me₂(DMAP)SiNIPr]⁺ moiety. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

▼ Show Figures

Graphical abstract

15 pages, 1155 KiB

Open AccessArticle

Synthesis and Biological Evaluation of N- Pyrazolyl Derivatives and Pyrazolopyrimidine Bearing a Biologically Active Sulfonamide Moiety as Potential Antimicrobial Agent

by Hend N. Hafez^1,2,* and Abdel-Rhman B.A. El-Gazzar^1,2

¹ Department of Chemistry, College of Science, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box: 90950 Riyadh 11623, Saudi Arabia

² Photochemistry Department, Heterocyclic & Nucleosides Unit, National Research Centre, Dokki, Giza 12622, Egypt

Molecules 2016, 21(9), 1156; https://doi.org/10.3390/molecules21091156 - 31 Aug 2016

Cited by 18 | Viewed by 6541

Abstract

A series of novel pyrazole-5-carboxylate containing N-triazole derivatives 3,4; different heterocyclic amines 7a–b and 10a–b; pyrazolo[4,3-d]pyrimidine containing sulfa drugs 14a,b; and oxypyrazolo[4,3-d]pyrimidine derivatives 17, 19, [...] Read more.

A series of novel pyrazole-5-carboxylate containing N-triazole derivatives 3,4; different heterocyclic amines 7a–b and 10a–b; pyrazolo[4,3-d]pyrimidine containing sulfa drugs 14a,b; and oxypyrazolo[4,3-d]pyrimidine derivatives 17, 19, 21 has been synthesized. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. All compounds have been screened for their in vitro antimicrobial activity against three gram-positive and gram-negative bacteria as well as three fungi. The results revealed that compounds 14b and 17 had more potent antibacterial activity against all bacterial strains than reference drug Cefotaxime. Moreover compounds 4, 7b, and 12b showed excellent antifungal activities against Aspergillus niger and Candida albicans in low inhibitory concentrations but slightly less than the reference drug miconazole against Aspergillus flavus. Full article

▼ Show Figures

Graphical abstract

24 pages, 26838 KiB

Open AccessArticle

Identification of Iridoids in Edible Honeysuckle Berries (Lonicera caerulea L. var. kamtschatica Sevast.) by UPLC-ESI-qTOF-MS/MS

by Alicja Z. Kucharska^1,*

and Izabela Fecka²

¹ Department of Fruit and Vegetables and Cereals Technology, Wrocław University of Environmental and Life Science, Chełmońskiego 37, 51-630 Wrocław, Poland

² Department of Pharmacognosy, Wrocław Medical University, Borowska 211A, 50-556 Wrocław, Poland

Molecules 2016, 21(9), 1157; https://doi.org/10.3390/molecules21091157 - 1 Sep 2016

Cited by 44 | Viewed by 8600

Abstract

Iridoid profiles of honeysuckle berry were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry UPLC-ESI-qTOF-MS/MS in positive and negative ions mode. The MS fragmentation pathways of detected iridoid glycosides were also studied in both modes. In the [...] Read more.

Iridoid profiles of honeysuckle berry were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry UPLC-ESI-qTOF-MS/MS in positive and negative ions mode. The MS fragmentation pathways of detected iridoid glycosides were also studied in both modes. In the negative ESI mass spectra, iridoids with a methyl ester or lactone structure have preferentially produced adduct [M + HCOOH − H]⁻ ions. However, protonated ions of molecular fragments, which were released by glycosidic bond cleavage and following fragmentation of aglycone rings, were more usable for iridoid structure analysis. In addition, the neutral losses of H₂O, CO, CO₂, CH₃OH, acetylene, ethenone and cyclopropynone have provided data confirming the presence of functional substituents in the aglycone. Among the 13 iridoids, 11 were identified in honeysuckle berries for the first time: pentosides of loganic acid (two isomers), pentosides of loganin (three isomers), pentosyl sweroside, and additionally 7-epi-loganic acid, 7-epi-loganin, sweroside, secologanin, and secoxyloganin. The five pentoside derivatives of loganic acid and loganin have not been previously detected in the analyzed species. Honeysuckle berries are a source of iridoids with different structures, compounds that are rarely present in fruits. Full article

▼ Show Figures

Graphical abstract

10 pages, 2238 KiB

Open AccessArticle

Icariin Metabolism by Human Intestinal Microflora

by Hailong Wu, Mihyang Kim and Jaehong Han^*

Metalloenzyme Research Group and Department of Integrative Plant Science, Chung-Ang University, Anseong 17546, Korea

Molecules 2016, 21(9), 1158; https://doi.org/10.3390/molecules21091158 - 31 Aug 2016

Cited by 72 | Viewed by 8601

Abstract

Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information [...] Read more.

Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

▼ Show Figures

Graphical abstract

16 pages, 4654 KiB

Open AccessArticle

Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies

by Yung-Yi Cheng¹

and Tung-Hu Tsai^1,2,3,4,5,*

¹ Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan

² Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan

³ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁴ Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan

⁵ Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan

Molecules 2016, 21(9), 1159; https://doi.org/10.3390/molecules21091159 - 1 Sep 2016

Cited by 11 | Viewed by 6727

Abstract

Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem [...] Read more.

Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was used to measure the herbal biomarkers of ginsenoside Rb₁, Rb₂, Rc, Rd, Re, Rg₁, Rh₁, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP), water solubility index (WSI), and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

21 pages, 5737 KiB

Open AccessArticle

Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added ¹⁸F-Labelling Methods

by Christian Drerup

, Johannes Ermert^*

and Heinz H. Coenen

Institut für Neurowissenschaften und Medizin, INM-5: Nuklearchemie, Forschungszentrum Jülich, 52425 Jülich, Germany

Molecules 2016, 21(9), 1160; https://doi.org/10.3390/molecules21091160 - 1 Sep 2016

Cited by 11 | Viewed by 6403

Abstract

Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and [...] Read more.

Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and ¹⁸F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be ¹⁸F-labelled in no-carrier-added (n.c.a.) form. For preparation of the ¹⁸F-labelled nNOS-Inhibitor [¹⁸F]10 a “build-up” radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [¹⁸F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified “late-stage” ¹⁸F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. ¹⁸F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [¹⁸F]10 as probe for preclinical in vivo studies. Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Figure 1

16 pages, 847 KiB

Open AccessArticle

Extracts from Traditional Chinese Medicinal Plants Inhibit Acetylcholinesterase, a Known Alzheimer’s Disease Target

by Dorothea Kaufmann^1,*

, Anudeep Kaur Dogra², Ahmad Tahrani¹, Florian Herrmann¹ and Michael Wink¹

¹ Institute of Pharmacy and Molecular Biotechnology, Department of Biology, Ruprecht Karls University Heidelberg, Heidelberg 69120, Germany

² Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK

Molecules 2016, 21(9), 1161; https://doi.org/10.3390/molecules21091161 - 31 Aug 2016

Cited by 85 | Viewed by 11216

Abstract

Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer’s Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro [...] Read more.

Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer’s Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman’s colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei), Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE. The methanol and aqueous extracts of Coptis chinensis showed IC₅₀ values of 0.031 µg/mL and 2.5 µg/mL, therefore having an up to 100-fold stronger AChE inhibitory activity than the already known AChE inhibitor galantamine (IC₅₀ = 4.33 µg/mL). Combinations of individual alkaloids berberine, coptisine and palmatine resulted in a synergistic enhancement of ACh inhibition. Therefore, the mode of AChE inhibition of crude extracts of Coptis chinensis, Berberis bealei and Phellodendron chinense is probably due to of this synergism of isoquinoline alkaloids. All extracts were also tested for their cytotoxicity in COS7 cells and none of the most active extracts was cytotoxic at the concentrations which inhibit AChE. Based on these results it can be stated that some TCM plants inhibit AChE via synergistic interaction of their secondary metabolites. The possibility to isolate pure lead compounds from the crude extracts or to administer these as nutraceuticals or as cheap alternative to drugs in third world countries make TCM plants a versatile source of natural inhibitors of AChE. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

▼ Show Figures

Figure 1

16 pages, 687 KiB

Open AccessArticle

Comparison of the Essential Oil Composition of Selected Impatiens Species and Its Antioxidant Activities

by Katarzyna Szewczyk^1,*

, Danuta Kalemba²

, Łukasz Komsta³ and Renata Nowak¹

¹ Department of Pharmaceutical Botany, Medical University of Lublin, Chodźki 1 St., 20-093 Lublin, Poland

² Institute of General Food Chemistry, Lodz University of Technology, Stefanowskiego 4/10 St., 90-924 Łódź, Poland

³ Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland

Molecules 2016, 21(9), 1162; https://doi.org/10.3390/molecules21091162 - 1 Sep 2016

Cited by 23 | Viewed by 5813

Abstract

The present paper describes the chemical composition of the essential oils obtained by hydrodistillation from four Impatiens species, Impatiens glandulifera Royle, I. parviflora DC., I. balsamina L. and I. noli-tangere L. The GC and GC-MS methods resulted in identification of 226 volatile compounds [...] Read more.

The present paper describes the chemical composition of the essential oils obtained by hydrodistillation from four Impatiens species, Impatiens glandulifera Royle, I. parviflora DC., I. balsamina L. and I. noli-tangere L. The GC and GC-MS methods resulted in identification of 226 volatile compounds comprising from 61.7%–88.2% of the total amount. The essential oils differed significantly in their composition. Fifteen compounds were shared among the essential oils of all investigated Impatiens species. The majority of these constituents was linalool (0.7%–15.1%), hexanal (0.2%–5.3%) and benzaldehyde (0.1%–10.2%). Moreover, the antioxidant activity of the essential oils was investigated using different methods. The chemical composition of the essential oils and its antioxidant evaluation are reported for the first time from the investigated taxon. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

12 pages, 2394 KiB

Open AccessReview

Small Molecule-Photoactive Yellow Protein Labeling Technology in Live Cell Imaging

by Feng Gao^1,2, Tang Gao³, Kechao Zhou^1,* and Wenbin Zeng^3,*

¹ Powder Metallurgy Research Institute of Central South University, Changsha 410013, China

² The Third Xiangya Hospital, Central South University, Changsha 410013, China

³ School of Pharmaceutical Sciences, Central South University, Changsha 410013, China

Molecules 2016, 21(9), 1163; https://doi.org/10.3390/molecules21091163 - 31 Aug 2016

Cited by 7 | Viewed by 8557

Abstract

Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro [...] Read more.

Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro and in live cells or in vivo. A peptide or a protein tag fused to the protein of interest and provides the opportunities for an attachment of small molecule probes or other fluorophore to image the dynamics of protein localization. Here we reviewed the recent development of no-wash small molecular probes for photoactive yellow protein (PYP-tag), by the means of utilizing a quenching mechanism based on the intramolecular interactions, or an environmental-sensitive fluorophore. Several fluorogenic probes have been developed, with fast labeling kinetics and cell permeability. This technology allows quick live-cell imaging of cell-surface and intracellular proteins without a wash-out procedure. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Figure 1

14 pages, 949 KiB

Open AccessArticle

Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [¹⁸F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ₁ Receptors

by Mathias Kranz^1,†

, Bernhard Sattler^2,†

, Nathanael Wüst², Winnie Deuther-Conrad¹

, Marianne Patt², Philipp M. Meyer²

, Steffen Fischer¹, Cornelius K. Donat^1,3, Bernhard Wünsch⁴, Swen Hesse^2,5, Jörg Steinbach¹

, Peter Brust^1,*,†

and Osama Sabri^2,†

¹ Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany

² Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany

³ Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London SW7 2AZ, UK

⁴ Pharmaceutical and Medicinal Chemistry, University Münster, Münster 48149, Germany

⁵ Integrated Research and Treatment Center (IFB) Adiposity Diseases, University Hospital Leipzig, Leipzig 04103, Germany

Molecules 2016, 21(9), 1164; https://doi.org/10.3390/molecules21091164 - 1 Sep 2016

Cited by 32 | Viewed by 7239

Abstract

The enantiomers of [¹⁸F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[¹⁸F]fluspidine and ( [...] Read more.

The enantiomers of [¹⁸F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[¹⁸F]fluspidine and (R)-(+)-[¹⁸F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(−)-[¹⁸F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(−)-[¹⁸F]fluspidine and (R)-(+)-[¹⁸F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(−)-[¹⁸F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [¹⁸F]fluspidine enantiomers determined from the preclinical studies are comparable with other ¹⁸F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(−)-[¹⁸F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(−)-[¹⁸F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Graphical abstract

21 pages, 1197 KiB

Open AccessReview

Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases

by Clara Herrera-Arozamena¹, Olaia Martí-Marí¹

, Martín Estrada¹

, Mario De la Fuente Revenga² and María Isabel Rodríguez-Franco^1,*

¹ Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain

² Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA

Molecules 2016, 21(9), 1165; https://doi.org/10.3390/molecules21091165 - 1 Sep 2016

Cited by 33 | Viewed by 11093

Abstract

The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever [...] Read more.

The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer’s disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2). Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

▼ Show Figures

Figure 1

11 pages, 3432 KiB

Open AccessArticle

Single-Walled Carbon-Nanotubes-Based Organic Memory Structures

by Sundes Fakher^1,†, Razan Nejm², Ahmad Ayesh³, Amal AL-Ghaferi⁴, Dagou Zeze^5,‡ and Mohammed Mabrook^1,*

¹ School of Electronic Engineering, Bangor University, Dean Street, Bangor LL57 1UT, UK

² Department of Electrical Engineering, United Arab Emirates University, Al Ain, UAE

³ Department of Mathematics, Statistics and Physics, Qatar University, Doha, Qatar

⁴ Masdar Institute, Abu Dhabi, UAE

⁵ School of Engineering and Computing Sciences, Durham University, Durham DH1 3LE, UK

Molecules 2016, 21(9), 1166; https://doi.org/10.3390/molecules21091166 - 2 Sep 2016

Cited by 9 | Viewed by 6304

Abstract

The electrical behaviour of organic memory structures, based on single-walled carbon-nanotubes (SWCNTs), metal–insulator–semiconductor (MIS) and thin film transistor (TFT) structures, using poly(methyl methacrylate) (PMMA) as the gate dielectric, are reported. The drain and source electrodes were fabricated by evaporating 50 nm gold, and [...] Read more.

The electrical behaviour of organic memory structures, based on single-walled carbon-nanotubes (SWCNTs), metal–insulator–semiconductor (MIS) and thin film transistor (TFT) structures, using poly(methyl methacrylate) (PMMA) as the gate dielectric, are reported. The drain and source electrodes were fabricated by evaporating 50 nm gold, and the gate electrode was made from 50 nm-evaporated aluminium on a clean glass substrate. Thin films of SWCNTs, embedded within the insulating layer, were used as the floating gate. SWCNTs-based memory devices exhibited clear hysteresis in their electrical characteristics (capacitance–voltage (C–V) for MIS structures, as well as output and transfer characteristics for transistors). Both structures were shown to produce reliable and large memory windows by virtue of high capacity and reduced charge leakage. The hysteresis in the output and transfer characteristics, the shifts in the threshold voltage of the transfer characteristics, and the flat-band voltage shift in the MIS structures were attributed to the charging and discharging of the SWCNTs floating gate. Under an appropriate gate bias (1 s pulses), the floating gate is charged and discharged, resulting in significant threshold voltage shifts. Pulses as low as 1 V resulted in clear write and erase states. Full article

(This article belongs to the Special Issue Organic Memory Devices)

▼ Show Figures

Graphical abstract

10 pages, 736 KiB

Open AccessArticle

Tetranortriterpenes and Limonoids from the Roots of Aphanamixis polystachya

by Ching-Jie Lin¹, I-Wen Lo¹, Yu-Chi Lin², Shun-Ying Chen³, Ching-Te Chien³, Yao-Haur Kuo⁴, Tsong-Long Hwang^5,6

, Shorong-Shii Liou⁷ and Ya-Ching Shen^1,*

¹ School of Pharmacy, College of Medicine, National Taiwan University, No. 33, Linsen S. Rd., Zhongzheng Dist., Taipei 10050, Taiwan

² Department of Life Sciences, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan

³ Taiwan Forestry Research Institute, Council of Agriculture, Executive Yuan, No. 53, Nanhai Rd., Zhongzheng Dist., Taipei 10066, Taiwan

⁴ National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No. 155-1, Sec. 2, Linong St., Beitou District, Taipei 11221, Taiwan

⁵ Graduate Institute of Natural Products, School of Traditional Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan

⁶ Department of Cosmetic Science and Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan

⁷ Department of Pharmacy, Tajen University, No. 20, Weixin Rd., Yanpu Township, Pingtung 90741, Taiwan

Molecules 2016, 21(9), 1167; https://doi.org/10.3390/molecules21091167 - 2 Sep 2016

Cited by 10 | Viewed by 6286

Abstract

Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (1–4) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known [...] Read more.

Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (1–4) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known limonoids (rohituka 3 (6), rohituka 7 (7), nymania 1 (8), rubrin G (9), prieurianin (10)) and a steroid (2,3-dihydroxy-5-pregnan-16-one (11)). Their structures were determined by spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Cytotoxic and anti-inflammatory activities of these compounds were evaluated. Compounds 4 and 5 showed significant inhibition against superoxide generation and elastase release by human neutrophils in response to (formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B) (FMLP/CB). Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

▼ Show Figures

Figure 1

13 pages, 1748 KiB

Open AccessArticle

¹³C-NMR-Based Metabolomic Profiling of Typical Asian Soy Sauces

by Ghulam Mustafa Kamal^1,2, Bin Yuan^1,2, Abdullah Ijaz Hussain³, Jie Wang¹, Bin Jiang¹, Xu Zhang^1,* and Maili Liu^1,*

¹ Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China

² University of Chinese Academy of Sciences, Beijing 100049, China

³ Institute of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan

Molecules 2016, 21(9), 1168; https://doi.org/10.3390/molecules21091168 - 2 Sep 2016

Cited by 18 | Viewed by 7310

Abstract

It has been a strong consumer interest to choose high quality food products with clear information about their origin and composition. In the present study, a total of 22 Asian soy sauce samples have been analyzed in terms of ¹³C-NMR spectroscopy. Spectral [...] Read more.

It has been a strong consumer interest to choose high quality food products with clear information about their origin and composition. In the present study, a total of 22 Asian soy sauce samples have been analyzed in terms of ¹³C-NMR spectroscopy. Spectral data were analyzed by multivariate statistical methods in order to find out the important metabolites causing the discrimination among typical soy sauces from different Asian regions. It was found that significantly higher concentrations of glutamate in Chinese red cooking (CR) soy sauce may be the result of the manual addition of monosodium glutamate (MSG) in the final soy sauce product. Whereas lower concentrations of amino acids, like leucine, isoleucine and valine, observed in CR indicate the different fermentation period used in production of CR soy sauce, on the other hand, the concentration of some fermentation cycle metabolites, such as acetate and sucrose, can be divided into two groups. The concentrations of these fermentation cycle metabolites were lower in CR and Singapore Kikkoman (SK), whereas much higher in Japanese shoyu (JS) and Taiwan (China) light (TL), which depict the influence of climatic conditions. Therefore, the results of our study directly indicate the influences of traditional ways of fermentation, climatic conditions and the selection of raw materials and can be helpful for consumers to choose their desired soy sauce products, as well as for researchers in further authentication studies about soy sauce. Full article

(This article belongs to the Section Metabolites)

▼ Show Figures

Graphical abstract

11 pages, 2876 KiB

Open AccessArticle

Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1

by Hee-Sung Chae, Young-Mi Kim and Young-Won Chin^*

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea

Molecules 2016, 21(9), 1169; https://doi.org/10.3390/molecules21091169 - 2 Sep 2016

Cited by 26 | Viewed by 7462 | Correction

Abstract

Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to [...] Read more.

Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1. In addition, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phospholipase C (PLC) gamma 1, and AKT phosphorylation relevant to NPM-ALK signal pathway were assessed. IL-6 levels in the HMC-1 stimulated by phorbol-12-myristate-13-acetate and A23187 were apparently decreased by the treatment of atractylodin. Concurrently, atractylodin not only inhibited the phosphorylation of NPM-ALK, but also suppressed the phosphorylation of JAK2, STAT3, PLC gamma 1, and AKT. Furthermore, the activated mitogen-activated protein kinases (MAPKs) by phorbol-12-myristate-13-acetate and A23187 were inhibited by atractylodin. These results suggested that atractylodin might have a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

▼ Show Figures

Figure 1

3 pages, 161 KiB

Open AccessCommentary

The Search for Covalently Ligandable Proteins in Biological Systems

by Syed Lal Badshah^1,2,*

and Yahia Nasser Mabkhot³

¹ Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan

² Department of Biochemistry, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa 25120, Pakistan

³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(9), 1170; https://doi.org/10.3390/molecules21091170 - 2 Sep 2016

Cited by 1 | Viewed by 4521

Abstract

This commentary highlights the recent article published in Nature, June 2016, titled: “Proteome-wide covalent ligand discovery in native biological systems”. They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found [...] Read more.

This commentary highlights the recent article published in Nature, June 2016, titled: “Proteome-wide covalent ligand discovery in native biological systems”. They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here. Full article

(This article belongs to the Section Medicinal Chemistry)

14 pages, 9478 KiB

Open AccessArticle

Characterization of Antifungal Natural Products Isolated from Endophytic Fungi of Finger Millet (Eleusine coracana)

by Walaa Kamel Mousa^1,2, Adrian L. Schwan³ and Manish N. Raizada^1,*

¹ Department of Plant Agriculture, University of Guelph, Guelph, ON N1G 2W1, Canada

² Department of Pharmacognosy, Mansoura University, Mansoura 35516, Egypt

³ Department of Chemistry, University of Guelph, Guelph, ON N1G 2W1, Canada

Molecules 2016, 21(9), 1171; https://doi.org/10.3390/molecules21091171 - 3 Sep 2016

Cited by 21 | Viewed by 10264

Abstract

Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti- [...] Read more.

Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-Fusarium activity. However, active compounds were isolated from only one strain. The objectives of this study were to confirm the endophytic lifestyle of the three remaining anti-Fusarium isolates, to identify the major underlying antifungal compounds, and to initially characterize the mode(s) of action of each compound. Results of confocal microscopy and a plant disease assay were consistent with the three fungal strains behaving as endophytes. Using bio-assay guided fractionation and spectroscopic structural elucidation, three anti-Fusarium secondary metabolites were purified and characterized. These molecules were not previously reported to derive from fungi nor have antifungal activity. The purified antifungal compounds were: 5-hydroxy 2(3H)-benzofuranone, dehydrocostus lactone (guaianolide sesquiterpene lactone), and harpagoside (an iridoide glycoside). Light microscopy and vitality staining were used to visualize the in vitro interactions between each compound and Fusarium; the results suggested a mixed fungicidal/fungistatic mode of action. We conclude that finger millet possesses fungal endophytes that can synthesize anti-fungal compounds not previously reported as bio-fungicides against F. graminearum. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

13 pages, 1028 KiB

Open AccessReview

The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

by Krithika Srikanthan¹, Joseph I. Shapiro¹ and Komal Sodhi^2,*

¹ Department of Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA

² Department of Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA

Molecules 2016, 21(9), 1172; https://doi.org/10.3390/molecules21091172 - 3 Sep 2016

Cited by 70 | Viewed by 9668

Abstract

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the [...] Read more.

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS. Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

▼ Show Figures

Figure 1

10 pages, 1109 KiB

Open AccessCommunication

Effects of Substitution on Solid-State Fluorescence in 9-Aryl-9-methyl-9H-9-silafluorenes

by Yoshinori Yamanoi^*, Takayuki Nakashima, Masaki Shimada, Hiroaki Maeda and Hiroshi Nishihara^*

Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Molecules 2016, 21(9), 1173; https://doi.org/10.3390/molecules21091173 - 3 Sep 2016

Cited by 4 | Viewed by 6364

Abstract

Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9′-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 1–7 and a 9,9′-phenylene substituted one [...] Read more.

Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9′-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 1–7 and a 9,9′-phenylene substituted one (compound 8) and they exhibited similar absorption and emission spectra. The 9H-9-silafluorene 10 containing a 5,5′-(2,2′-bithiophenyl) group showed a significantly red-shifted absorption and fluorescence maxima in the solid-state. Single-crystal X-ray diffraction studies found J-type aggregated structures formed by intermolecular CH–π interactions (ca. 2.6–2.7 Å). Density functional theory (DFT), time-dependent DFT (TD-DFT), and configuration interaction single (CIS) calculations were conducted to explain the observed optical properties. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

▼ Show Figures

Graphical abstract

43 pages, 5497 KiB

Open AccessReview

Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC)

by Alessandro Mandoli^1,2

¹ Dipartimento di Chimica e Chimica Industriale Università di Pisa, Via G. Moruzzi 13, Pisa 56124, Italy

² ISTM-CNR, Via C. Golgi 19, Milano 20133, Italy

Molecules 2016, 21(9), 1174; https://doi.org/10.3390/molecules21091174 - 5 Sep 2016

Cited by 86 | Viewed by 11168

Abstract

The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are [...] Read more.

The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

▼ Show Figures

Figure 1

8 pages, 2572 KiB

Open AccessArticle

C19-Norditerpenoid Alkaloids from Aconitum szechenyianum and Their Effects on LPS-Activated NO Production

by Fei Wang, Zhenggang Yue^*,†, Pei Xie^†, Li Zhang, Zhen Li, Bei Song, Zhishu Tang and Xiaomei Song^*

Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi Rheumatism and Tumor Center of TCM Engineering Technology Research, School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China

Molecules 2016, 21(9), 1175; https://doi.org/10.3390/molecules21091175 - 3 Sep 2016

Cited by 24 | Viewed by 6452

Abstract

Three new C₁₉-norditerpenoid alkaloids (1–3), along with two known C₁₉-norditerpenoid alkaloids (4–5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as [...] Read more.

Three new C₁₉-norditerpenoid alkaloids (1–3), along with two known C₁₉-norditerpenoid alkaloids (4–5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1–5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC₅₀ value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

▼ Show Figures

Graphical abstract

21 pages, 7285 KiB

Open AccessReview

Synthesis Approaches to (−)-Cytoxazone, a Novel Cytokine Modulator, and Related Structures

by Izabel L. Miranda¹, Ítala K. B. Lopes¹, Marisa A. N. Diaz² and Gaspar Diaz^1,*

¹ Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil

² Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa 36570-000, Brazil

Molecules 2016, 21(9), 1176; https://doi.org/10.3390/molecules21091176 - 6 Sep 2016

Cited by 16 | Viewed by 9041

Abstract

(−)-Cytoxazone, originally isolated from cultures of a Streptomyces species has an oxazolidin-2-one 4,5-disubstituted ring. It is known that this natural product presents a cytokine modulator effect through the signaling pathway of Th2 cells (type 2 cytokines), which are involved in the process of [...] Read more.

(−)-Cytoxazone, originally isolated from cultures of a Streptomyces species has an oxazolidin-2-one 4,5-disubstituted ring. It is known that this natural product presents a cytokine modulator effect through the signaling pathway of Th2 cells (type 2 cytokines), which are involved in the process of growth and differentiation of cells. From this, the interest in the development of research aimed at the total synthesis of this molecule and its analogs has remained high, which can be confirmed by the large number of publications on the topic, more than 30 to date. This review focuses on the various creative methods for the synthesis of (−)-cytoxazone and its congeners. The assessment of the preparation of this oxazolidinone and related structures serves as a treatise on the efforts made in the synthesis of this important class of compound from its first total synthesis in 1999. Full article

▼ Show Figures

Graphical abstract

8 pages, 1344 KiB

Open AccessArticle

Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant

by Rong Shen, Taichi Kusakabe, Tomofumi Yatsu, Yuichiro Kanno

, Keisuke Takahashi, Kiyomitsu Nemoto

and Keisuke Kato^*

Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan

Molecules 2016, 21(9), 1177; https://doi.org/10.3390/molecules21091177 - 5 Sep 2016

Cited by 8 | Viewed by 5985

Abstract

An efficient Pd^II/Pd⁰-p-benzoquinone/hydroquinone-CuCl₂/CuCl catalyst system was developed that uses environmentally friendly molecular oxygen as the terminal oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides. Full article

(This article belongs to the Section Green Chemistry)

▼ Show Figures

Graphical abstract

11 pages, 2762 KiB

Open AccessArticle

Molecular Encapsulation of Histamine H₂-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study

by Hang Yin, Runmiao Wang, Jianbo Wan, Ying Zheng

, Defang Ouyang and Ruibing Wang^*

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China

Molecules 2016, 21(9), 1178; https://doi.org/10.3390/molecules21091178 - 6 Sep 2016

Cited by 6 | Viewed by 7212

Abstract

The histamine H₂-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10³ M⁻¹, 1.30 (±0.27) × 10⁴ M⁻¹ and 1.05 (±0.33) × 10⁵ M [...] Read more.

The histamine H₂-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10³ M⁻¹, 1.30 (±0.27) × 10⁴ M⁻¹ and 1.05 (±0.33) × 10⁵ M⁻¹, respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by ¹H-NMR, UV-visible spectroscopic titrations (including Job plots), electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC), as well as theoretically by molecular dynamics (MD) computation. This study may provide important insights on the supramolecular formulation of H₂-receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

▼ Show Figures

Figure 1

20 pages, 1306 KiB

Open AccessReview

A Review on the Terpenes from Genus Vitex

by Jin-Long Yao^1,2,†, Shi-Ming Fang^1,2,†, Rui Liu^1,3, Mahmood Brobbey Oppong¹, Er-Wei Liu^1,2, Guan-Wei Fan^1,2,* and Han Zhang^1,2,*

¹ Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

² Key Laboratory of Formula of Traditional Chinese Medicine of Ministry of Education, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

³ School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

Molecules 2016, 21(9), 1179; https://doi.org/10.3390/molecules21091179 - 6 Sep 2016

Cited by 49 | Viewed by 10240

Abstract

The genus Vitex, which belongs to the Verbenaceae family, includes approximately 250 species. Some species of the genus Vitex have traditionally been used for the treatment of headaches, ophthalmodynia, coughs, asthma, premenopausal syndrome, etc. Chemical investigations indicate that the characteristic constituents of the [...] Read more.

The genus Vitex, which belongs to the Verbenaceae family, includes approximately 250 species. Some species of the genus Vitex have traditionally been used for the treatment of headaches, ophthalmodynia, coughs, asthma, premenopausal syndrome, etc. Chemical investigations indicate that the characteristic constituents of the genus Vitex are terpenes, and 210 of these compounds, including monoterpenoids, sesquiterpenoids, diterpenoids and triterpenoids, have been obtained from 12 species. Pharmacological studies had shown that these terpenes possess anti-inflammatory, antitumor, antibacterial, antioxidant activities, and so on. In this paper, the identity of these terpenes and their pharmacological effects are reviewed, which can provide references for further research regarding the chemistry and utilization of the Vitex species. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

12 pages, 4279 KiB

Open AccessArticle

Biphenyl Phytoalexin in Sorbus pohuashanensis Suspension Cell Induced by Yeast Extract

by Liangyun Zhou^1,†, Jian Yang^1,†, Guang Yang¹, Chuanzhi Kang¹, Wenjuan Xiao², Chaogeng Lv¹, Sheng Wang¹

, Jinfu Tang¹ and Lanping Guo^1,*

¹ The State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

² Pixian Chinese Medicine Hospital, Chengdu 611730, China

Molecules 2016, 21(9), 1180; https://doi.org/10.3390/molecules21091180 - 14 Sep 2016

Cited by 19 | Viewed by 4766

Abstract

Biphenyls are unique phytoalexins de novo synthesized in plants in response to pathogen attack. These compounds are found in Maloideae, a subfamily of the Rosaceae. The anti-microbial activities of biphenyls have been reported in a number of studies and they appear to represent [...] Read more.

Biphenyls are unique phytoalexins de novo synthesized in plants in response to pathogen attack. These compounds are found in Maloideae, a subfamily of the Rosaceae. The anti-microbial activities of biphenyls have been reported in a number of studies and they appear to represent an important defense strategy against pathogens common in the Maloideae, such as species in Malus, Pyrus, Sorbus, and Chaenomeles. Here, cell suspension cultures of Sorbus pohuashanensis were established to study biphenyl phytoalexins formation after yeast extract (YE) treatment. An ultra-performance liquid chromatography (UPLC) method coupled with quadrupole time of flight mass spectrometry (Q-TOF-MS) LC−MS/MS was applied to determine the time course of these biphenyl biomarkers accumulation in YE-treated S. pohuashanensis suspension cells. The results of quantitative analyses show the content of Noraucuparin, 2′-Hydroxyaucuparin, and their glycosides initially increased, then decreased over time. The Noraucuparin content reached its highest (225.76 μg·g⁻¹) at 18 h after treatment, 6 hours earlier than that of Noraucuparin 5-O-β-d-glucopyranoside. The content of 2′-Hydroxyaucuparin reached its highest (422.75 μg·g⁻¹) at 30 h after treatment, also earlier than that of its glycoside. The understanding of phytoalexin metabolism in this study may provide a basis for improving Maloideae resistance to pathogens. Full article

▼ Show Figures

Figure 1

11 pages, 3263 KiB

Open AccessArticle

Structural Features of Alkaline Extracted Polysaccharide from the Seeds of Plantago asiatica L. and Its Rheological Properties

by Jun-Yi Yin^1,†, Hai-Hong Chen^1,†, Hui-Xia Lin², Ming-Yong Xie¹ and Shao-Ping Nie^1,*

¹ State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China

² Xiamen Huaxia College, Xiamen 361024, China

Molecules 2016, 21(9), 1181; https://doi.org/10.3390/molecules21091181 - 6 Sep 2016

Cited by 28 | Viewed by 6074

Abstract

Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but few papers report on the structural and rheological characteristics of the alkaline extract. The alkaline extracted polysaccharide was prepared from seeds of P. asiatica L. and named herein as alkaline extracted [...] Read more.

Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but few papers report on the structural and rheological characteristics of the alkaline extract. The alkaline extracted polysaccharide was prepared from seeds of P. asiatica L. and named herein as alkaline extracted polysaccharide from seeds of P. asiatica L. (PLAP). Its structural and rheological properties were characterized by monosaccharide composition, methylation, GC-MS and rheometry. PLAP, as an acidic arabinoxylan, was mainly composed of 1,2,4-linked Xylp and 1,3,4-linked Xylp residues. PLAP solution showed pseudoplastic behavior, and weak gelling properties at high concentration. Sodium and especially calcium ions played a significant role in increasing the apparent viscosity and gel strength. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

▼ Show Figures

Graphical abstract

9 pages, 1375 KiB

Open AccessArticle

Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported Chiral Picolinamides

by Sílvia D. Fernandes¹, Riccardo Porta^2,*, Pedro C. Barrulas¹, Alessandra Puglisi², Anthony J. Burke^1,*

and Maurizio Benaglia^2,*

¹ Department of Chemistry and Chemistry Center of Évora, School of Science and Technology and Institute for Research and Advanced Studies, University of Évora, Rua Romão Ramalho 59, Évora 7000, Portugal

² Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milano 20133, Italy

Molecules 2016, 21(9), 1182; https://doi.org/10.3390/molecules21091182 - 6 Sep 2016

Cited by 18 | Viewed by 6720

Abstract

The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials [...] Read more.

The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time, a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

▼ Show Figures

Figure 1

21 pages, 799 KiB

Open AccessReview

A Systematic Review on the Implication of Minerals in the Onset, Severity and Treatment of Periodontal Disease

by Alfonso Varela-López¹

, Francesca Giampieri²

, Pedro Bullón³, Maurizio Battino²

and José L. Quiles^1,*

¹ Department of Physiology, Institute of Nutrition and Food Technology “Jose Mataix”, University of Granada, Biomedical Research Center, Avda. Conocimiento s.n., 18100 Armilla, Granada, Spain

² Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, 60131 Ancona, Italy

³ Department of Stomalogy, Dental School, University of Sevilla, C/Avicena s.n., 41009 Sevilla, Andalusia, Spain

Molecules 2016, 21(9), 1183; https://doi.org/10.3390/molecules21091183 - 7 Sep 2016

Cited by 27 | Viewed by 8763

Abstract

Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The [...] Read more.

Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The role of nutrition in different chronic inflammatory diseases has been the subject of an increasing body of research in the last decades. In this sense, there has been an important increase in the volume of research on role of nutrition in periodontitis since the diet has known effects on the immune system and inflammatory cascades. Minerals play a key role in all these processes due to the multiple pathways where they participate. To clarify the role of the different minerals in the establishment, progression and/or treatment of this pathology, a systemically review of published literature cited in PubMed until May 2016 was conducted, which included research on the relationship of these elements with the onset and progression of periodontal disease. Among all the minerals, calcium dietary intake seems important to maintain alveolar bone. Likewise, dietary proportions of minerals that may influence its metabolism also can be relevant. Lastly, some observations suggest that all those minerals with roles in immune and/or antioxidant systems should be considered in future research. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

▼ Show Figures

Figure 1

12 pages, 2054 KiB

Open AccessArticle

Three Pairs of New Isopentenyl Dibenzo[b,e]oxepinone Enantiomers from Talaromyces flavus, a Wetland Soil-Derived Fungus

by Tian-Yu Sun^1,†, Run-Qiao Kuang^1,†, Guo-Dong Chen^1,*, Sheng-Ying Qin², Chuan-Xi Wang¹, Dan Hu¹, Bing Wu³, Xing-Zhong Liu³, Xin-Sheng Yao¹ and Hao Gao^1,*

¹ Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

² Clinical Experimental Center, First Affiliated Hospital of Jinan University, Guangzhou 510632, China

³ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China

Molecules 2016, 21(9), 1184; https://doi.org/10.3390/molecules21091184 - 7 Sep 2016

Cited by 15 | Viewed by 4894

Abstract

Three pairs of new isopentenyl dibenzo[b,e]oxepinone enantiomers, (+)-(5S)-arugosin K (1a), (−)-(5R)-arugosin K (1b), (+)-(5S)-arugosin L (2a), (−)-(5R)-arugosin L (2b), (+)-(5S)-arugosin M [...] Read more.

Three pairs of new isopentenyl dibenzo[b,e]oxepinone enantiomers, (+)-(5S)-arugosin K (1a), (−)-(5R)-arugosin K (1b), (+)-(5S)-arugosin L (2a), (−)-(5R)-arugosin L (2b), (+)-(5S)-arugosin M (3a), (−)-(5R)-arugosin M (3b), and a new isopentenyl dibenzo[b,e]oxepinone, arugosin N (4), were isolated from a wetland soil-derived fungus Talaromyces flavus, along with two known biosynthetically-related compounds 5 and 6. Among them, arugosin N (4) and 1,6,10-trihydroxy-8-methyl-2-(3-methyl-2-butenyl)-dibenz[b,e]oxepin-11(6H)-one (CAS: 160585-91-1, 5) were obtained as the tautomeric mixtures. The structures of isolated compounds were determined by detailed spectroscopic analysis. In addition, the absolute configurations of these three pairs of new enantiomers were determined by quantum chemical ECD calculations. Full article

▼ Show Figures

Figure 1

9 pages, 3443 KiB

Open AccessArticle

Boronic Acid Group: A Cumbersome False Negative Case in the Process of Drug Design

by Sotirios Katsamakas¹

, Anastasios G. Papadopoulos²

and Dimitra Hadjipavlou-Litina^1,*

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece

² Laboratory of Applied Quantum Chemistry, School of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece

Molecules 2016, 21(9), 1185; https://doi.org/10.3390/molecules21091185 - 7 Sep 2016

Cited by 12 | Viewed by 6621

Abstract

Herein we present, an exhaustive docking analysis considering the case of autotaxin (ATX). HA155, a small molecule inhibitor of ATX, is co-crystallized. In order to further extract conclusions on the nature of the bond formed between the ligands and the amino acid residues [...] Read more.

Herein we present, an exhaustive docking analysis considering the case of autotaxin (ATX). HA155, a small molecule inhibitor of ATX, is co-crystallized. In order to further extract conclusions on the nature of the bond formed between the ligands and the amino acid residues of the active site, density functional theory (DFT) calculations were undertaken. However, docking does not provide reproducible results when screening boronic acid derivatives and their binding orientations to protein drug targets. Based on natural bond orbital (NBO) calculations, the formed bond between Ser/Thr residues is characterized more accurately as a polar covalent bond instead of a simple nonpolar covalent one. The presented results are acceptable and could be used in screening as an active negative filter for boron compounds. The hydroxyl groups of amino acids are bonded with the inhibitor’s boron atom, converting its hybridization to sp³. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

▼ Show Figures

Graphical abstract

11 pages, 1372 KiB

Open AccessArticle

Catechins Variously Affect Activities of Conjugation Enzymes in Proliferating and Differentiated Caco-2 Cells

by Kateřina Lněničková¹

, Eliška Procházková¹, Lenka Skálová¹, Petra Matoušková¹

, Hana Bártíková¹, Pavel Souček² and Barbora Szotáková^1,*

¹ Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové CZ-50005, Czech Republic

² Toxicogenomics Unit, Centre of Toxicology and Health Safety, National Institute of Public Health, Prague CZ-10042, Czech Republic

Molecules 2016, 21(9), 1186; https://doi.org/10.3390/molecules21091186 - 7 Sep 2016

Cited by 6 | Viewed by 5910

Abstract

The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and [...] Read more.

The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and their modulation by green tea extract (GTE) and epigallocatechin gallate (EGCG) using both proliferating (P) and differentiated (D) caco-2 cells. The mRNA levels of the main conjugation enzymes were significantly elevated after the differentiation of Caco-2 cells. However, no increase in conjugation enzymes’ activities in differentiated cells was detected in comparison to proliferating ones. GTE/EGCG treatment did not affect the mRNA levels of any of the conjugation enzymes tested in either type of cells. Concerning conjugation enzymes activities, GTE/EGCG treatment elevated glutathione S-transferase (GST) activity by approx. 30% and inhibited catechol-O-methyltransferase (COMT) activity by approx. 20% in differentiated cells. On the other hand, GTE as well as EGCG treatment did not significantly affect the activities of conjugation enzymes in proliferating cells. Administration of GTE/EGCG mediated only mild changes of GST and COMT activities in enterocyte-like cells, indicating a low risk of GTE/EGCG interactions with concomitantly administered drugs. However, a considerable chemo-protective effect of GTE via the pronounced induction of detoxifying enzymes cannot be expected as well. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

▼ Show Figures

Figure 1

14 pages, 3810 KiB

Open AccessArticle

Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells

by Kyong-Hoon Choi¹, Ki Chang Nam²

, Leszek Malkinski³, Eun Ha Choi^1,4

, Jin-Seung Jung^5,* and Bong Joo Park^1,4,*

¹ Plasma Bioscience Research Center, Kwangwoon University, 20 Kwangwoongil, Nowon-gu, Seoul 01897, Korea

² Department of Medical Engineering, Dongguk University College of Medicine, Gyeonggi-do 10326, Korea

³ Advanced Materials Research Institute, University of New Orleans, New Orleans, LA 70148, USA

⁴ Department of Electrical & Biological Physics, Kwangwoon University, 20 Kwangwoongil, Nowon-gu, Seoul 01897, Korea

⁵ Department of Chemistry, Gangneung-Wonju National University, Gangneung 25457, Korea

Molecules 2016, 21(9), 1187; https://doi.org/10.3390/molecules21091187 - 6 Sep 2016

Cited by 16 | Viewed by 5582

Abstract

In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe₂O₄-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting [...] Read more.

In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe₂O₄-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe₂O₄) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe₂O₄ particles were finely adjusted by controlling the size of the primary CoFe₂O₄ nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe₂O₄-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe₂O₄-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe₂O₄-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism. Full article

(This article belongs to the Special Issue Photodynamic Therapy)

▼ Show Figures

Graphical abstract

23 pages, 1684 KiB

Open AccessReview

Bioprinting and Differentiation of Stem Cells

by Scott A. Irvine^*

and Subbu S. Venkatraman

School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore

Molecules 2016, 21(9), 1188; https://doi.org/10.3390/molecules21091188 - 8 Sep 2016

Cited by 117 | Viewed by 12609

Abstract

The 3D bioprinting of stem cells directly into scaffolds offers great potential for the development of regenerative therapies; in particular for the fabrication of organ and tissue substitutes. For this to be achieved; the lineage fate of bioprinted stem cell must be controllable. [...] Read more.

The 3D bioprinting of stem cells directly into scaffolds offers great potential for the development of regenerative therapies; in particular for the fabrication of organ and tissue substitutes. For this to be achieved; the lineage fate of bioprinted stem cell must be controllable. Bioprinting can be neutral; allowing culture conditions to trigger differentiation or alternatively; the technique can be designed to be stimulatory. Such factors as the particular bioprinting technique; bioink polymers; polymer cross-linking mechanism; bioink additives; and mechanical properties are considered. In addition; it is discussed that the stimulation of stem cell differentiation by bioprinting may lead to the remodeling and modification of the scaffold over time matching the concept of 4D bioprinting. The ability to tune bioprinting properties as an approach to fabricate stem cell bearing scaffolds and to also harness the benefits of the cells multipotency is of considerable relevance to the field of biomaterials and bioengineering. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

▼ Show Figures

Figure 1

15 pages, 844 KiB

Open AccessArticle

Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenyl)carbamoyl]naphthalen-2-yl Carbamates

by Tomas Gonec^1,*

, Sarka Pospisilova², Lucie Holanova³, Josef Stranik¹, Aneta Cernikova¹, Valeria Pudelkova², Jiri Kos¹, Michal Oravec⁴

, Peter Kollar³, Alois Cizek² and Josef Jampilek^5,*

¹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic

² Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic

³ Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic

⁴ Global Change Research Institute CAS, Belidla 986/4a, Brno 60300, Czech Republic

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, Bratislava 83232, Slovakia

Molecules 2016, 21(9), 1189; https://doi.org/10.3390/molecules21091189 - 7 Sep 2016

Cited by 10 | Viewed by 5566

Abstract

Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate [...] Read more.

Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA) and antimycobacterial (MICs = 21 µM) activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl), the activity was similar (MICs ca. 70 µM). Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD₅₀ >30 µM). The structure-activity relationships are discussed. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

▼ Show Figures

Graphical abstract

10 pages, 1702 KiB

Open AccessArticle

Isolation of α-Amylase Inhibitors from Kadsura longipedunculata Using a High-Speed Counter-Current Chromatography Target Guided by Centrifugal Ultrafiltration with LC-MS

by Yin Cen¹, Aiping Xiao², Xiaoqing Chen^1,* and Liangliang Liu^2,*

¹ College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, China

² Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, Hunan, China

Molecules 2016, 21(9), 1190; https://doi.org/10.3390/molecules21091190 - 7 Sep 2016

Cited by 17 | Viewed by 6668

Abstract

In this study, a high-speed counter-current chromatography (HSCCC) separation method target guided by centrifugal ultrafiltration with high-performance liquid chromatography-mass spectrometry (CU-LC-MS) was proposed. This method was used to analyze α-amylase inhibitors from Kadsura longipedunculata extract. According to previous screening with CU-LC-MS, two screened [...] Read more.

In this study, a high-speed counter-current chromatography (HSCCC) separation method target guided by centrifugal ultrafiltration with high-performance liquid chromatography-mass spectrometry (CU-LC-MS) was proposed. This method was used to analyze α-amylase inhibitors from Kadsura longipedunculata extract. According to previous screening with CU-LC-MS, two screened potential α-amylase inhibitors was successfully isolated from Kadsura longipedunculata extract using HSCCC under the optimized experimental conditions. The isolated two target compounds (with purities of 92.3% and 94.6%) were, respectively, identified as quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) based on the MS, UV, and ¹H-NMR spectrometry data. To verify the inhibition of screened compounds, the inhibitory activities of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) on α-amylase were tested, and it demonstrated that the experimental IC₅₀ values of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) were 28.8 and 12.5 μmol/L. These results proved that the hyphenated technique using CU-LC-MS and HSCCC was a rapid, competent, and reproductive method to screen and separate potential active compounds, like enzyme inhibitors from the extract of herbal medicines. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

▼ Show Figures

Graphical abstract

12 pages, 1536 KiB

Open AccessArticle

Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula

by Yueting Li^1,2, Yuan Lu¹, Jianchun Hu^1,3, Zipeng Gong¹, Wu Yang^1,3, Aimin Wang⁴, Jiang Zheng¹, Ting Liu¹, Tingting Chen^1,3, Jie Hu^1,3, Ling Mi^1,3, Yongjun Li⁴

, Yanyu Lan⁴ and Yonglin Wang^1,*

¹ Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China

² National Engineering Research Center of Miao’s Medicines, Guiyang 550004, China

³ School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China

⁴ Engineering Research Center for the Development and Applications of Ethnic Medicines and Traditional Chinese Medicine (TCM), Ministry of Education, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China

Molecules 2016, 21(9), 1191; https://doi.org/10.3390/molecules21091191 - 7 Sep 2016

Cited by 20 | Viewed by 5754

Abstract

Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. [...] Read more.

Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats. Plasma samples were collected at various time points after a single dose (intravenous, i.v.) of Xin-Shao formula. The levels of plasma scutellarin and paeoniflorin at the designed time points were determined by a UPLC-MS/MS method, and drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. Increase in terminal elimination half-life (t_1/2z) and mean residence time (MRT_(0–t)) of scutellarin as well as elevation in area under the plasma drug concentration-time curve from 0 h to the terminal time point (AUC_(0–t)) and maximum plasma drug concentration (C_max) of paeoniflorin, along with decreased clearance of paeoniflorin and scutellarin as well as reduced apparent volume of distribution (V_z) of paeoniflorin, were observed in MCAO rats, compared with those in sham-operated animals. The elimination of scutellarin and paeoniflorin were reduced in cerebral I/R injury reduced rats. Full article

▼ Show Figures

Graphical abstract

10 pages, 9446 KiB

Open AccessArticle

Effects of Culture Substrate Made of Poly(N-isopropylacrylamide-co-acrylic acid) Microgels on Osteogenic Differentiation of Mesenchymal Stem Cells

by Zhuojun Dai^1,*, Yinglan Shu², Chao Wan^2,* and Chi Wu¹

¹ Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

² Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Molecules 2016, 21(9), 1192; https://doi.org/10.3390/molecules21091192 - 9 Sep 2016

Cited by 14 | Viewed by 7231

Abstract

Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled [...] Read more.

Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled detachment of cells via temperature stimulus. Previous research about PNIPAM-based substrates mostly concentrated on their effects in cell adhesion and proliferation. In this study, however, we investigate the influence of the PNIPAM-based substrate on the differentiation capacity of stem cells. Especially, we choose P(NIPAM-AA) microgels as a culture dish coating and mesenchymal stem cells (MSCs) are cultured on top of the microgels. Interestingly, we find that the morphology of MSCs changes remarkably on a microgel-coated surface, from the original spindle form to a more stretched and elongated cell shape. Accompanied by the alternation in morphology, the expression of several osteogenesis-related genes is elevated even without inducing factors. In the presence of full osteogenic medium, MSCs on a microgel substrate show an enhancement in the expression level of osteopontin and alizarin red staining signals, indicating the physical property of substrate has a direct effect on MSCs differentiation. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

▼ Show Figures

Graphical abstract

14 pages, 5641 KiB

Open AccessArticle

NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

by Dahong Li¹, Xu Hu¹, Tong Han¹, Jie Liao¹, Wei Xiao^2,*, Shengtao Xu³, Zhanlin Li¹, Zhenzhong Wang², Huiming Hua^1,* and Jinyi Xu^3,*

¹ Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

² State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Processes, National Post-Doctoral Research Workstation, Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang 222001, China

³ State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

Molecules 2016, 21(9), 1193; https://doi.org/10.3390/molecules21091193 - 8 Sep 2016

Cited by 14 | Viewed by 5503

Abstract

A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a–i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, [...] Read more.

A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a–i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC₅₀ of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a–i also showed cytotoxic selectivity between tumor and normal liver cells with IC₅₀ ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

▼ Show Figures

Figure 1

13 pages, 8430 KiB

Open AccessArticle

Chemical Composition, Antibacterial Properties and Mechanism of Action of Essential Oil from Clove Buds against Staphylococcus aureus

by Jian-Guo Xu^1,2,*, Ting Liu², Qing-Ping Hu² and Xin-Ming Cao¹

¹ College of Food Sciences, Shanxi Normal University, Linfen 041004, China

² College of Life Sciences, Shanxi Normal University, Linfen 041004, China

Molecules 2016, 21(9), 1194; https://doi.org/10.3390/molecules21091194 - 8 Sep 2016

Cited by 215 | Viewed by 14807

Abstract

The essential oil of clove has a wide range of pharmacological and biological activities and is widely used in the medicine, fragrance and flavoring industries. In this work, 22 components of the essential oil obtained from clove buds were identified. Eugenol was the [...] Read more.

The essential oil of clove has a wide range of pharmacological and biological activities and is widely used in the medicine, fragrance and flavoring industries. In this work, 22 components of the essential oil obtained from clove buds were identified. Eugenol was the major component (76.23%). The essential oil exhibited strong antibacterial activity against Staphylococcus aureus ATCC 25923 with a minimum inhibitory concentration (MIC) of 0.625 mg/mL, and the antibacterial effects depended on its concentration and action time. Kill-time assays also confirmed the essential oil had a significant effect on the growth rate of surviving S. aureus. We hypothesized that the essential oil may interact with the cell wall and membrane first. On the one hand it destroys cell wall and membranes, next causing the losses of vital intracellular materials, which finally result in the bacterial death. Besides, essential oil penetrates to the cytoplasmic membrane or enters inside the cell after destruction of cell structure, and then inhibits the normal synthesis of DNA and proteins that are required for bacterial growth. These results suggested that the effects of the clove essential oil on the growth inhibition of S. aureus may be at the molecular level rather than only physical damage. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

12 pages, 2443 KiB

Open AccessArticle

Comparison of Protein N-Homocysteinylation in Rat Plasma under Elevated Homocysteine Using a Specific Chemical Labeling Method

by Tianzhu Zang¹, Ligi Paul Pottenplackel², Diane E. Handy³, Joseph Loscalzo³

, Shujia Dai¹, Richard C. Deth⁴, Zhaohui Sunny Zhou^1,* and Jisheng Ma^1,5,*

¹ Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA

² Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA

³ Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

⁴ Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33314, USA

⁵ School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China

Molecules 2016, 21(9), 1195; https://doi.org/10.3390/molecules21091195 - 8 Sep 2016

Cited by 6 | Viewed by 7937

Abstract

Elevated blood concentrations of homocysteine have been well established as a risk factor for cardiovascular diseases and neuropsychiatric diseases, yet the etiologic relationship of homocysteine to these disorders remains poorly understood. Protein N-homocysteinylation has been hypothesized as a contributing factor; however, it [...] Read more.

Elevated blood concentrations of homocysteine have been well established as a risk factor for cardiovascular diseases and neuropsychiatric diseases, yet the etiologic relationship of homocysteine to these disorders remains poorly understood. Protein N-homocysteinylation has been hypothesized as a contributing factor; however, it has not been examined globally owing to the lack of suitable detection methods. We recently developed a selective chemical method to label N-homocysteinylated proteins with a biotin-aldehyde tag followed by Western blotting analysis, which was further optimized in this study. We then investigated the variation of protein N-homocysteinylation in plasma from rats on a vitamin B₁₂ deficient diet. Elevated “total homocysteine” concentrations were determined in rats with a vitamin B₁₂ deficient diet. Correspondingly, overall levels of plasma protein N-homocysteinylation displayed an increased trend, and furthermore, more pronounced and statistically significant changes (e.g., 1.8-fold, p-value: 0.03) were observed for some individual protein bands. Our results suggest that, as expected, a general metabolic correlation exists between “total homocysteine” and N-homocysteinylation, although other factors are involved in homocysteine/homocysteine thiolactone metabolism, such as the transsulfuration of homocysteine by cystathionine β-synthase or the hydrolysis of homocysteine thiolactone by paraoxonase 1 (PON1), may play more significant or direct roles in determining the level of N-homocysteinylation. Full article

(This article belongs to the Section Bioorganic Chemistry)

▼ Show Figures

Graphical abstract

17 pages, 8657 KiB

Open AccessArticle

Immobilization of α-Amylase from Anoxybacillus sp. SK3-4 on ReliZyme and Immobead Supports

by Ummirul Mukminin Kahar¹, Mohd Helmi Sani¹, Kok-Gan Chan²

and Kian Mau Goh^1,*

¹ Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, Skudai 81310, Johor, Malaysia

² Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

Molecules 2016, 21(9), 1196; https://doi.org/10.3390/molecules21091196 - 9 Sep 2016

Cited by 28 | Viewed by 8565

Abstract

α-Amylase from Anoxybacillus sp. SK3-4 (ASKA) is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA) variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and [...] Read more.

α-Amylase from Anoxybacillus sp. SK3-4 (ASKA) is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA) variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and immobilized through covalent attachment on three epoxide (ReliZyme EP403/M, Immobead IB-150P, and Immobead IB-150A) and an amino-epoxide (ReliZyme HFA403/M) activated supports. Several parameters affecting immobilization were analyzed, including the pH, temperature, and quantity (mg) of enzyme added per gram of support. The influence of the carrier surface properties, pore sizes, and lengths of spacer arms (functional groups) on biocatalyst performances were studied. Free and immobilized TASKAs were stable at pH 6.0–9.0 and active at pH 8.0. The enzyme showed optimal activity and considerable stability at 60 °C. Immobilized TASKA retained 50% of its initial activity after 5–12 cycles of reuse. Upon degradation of starches and amylose, only immobilized TASKA on ReliZyme HFA403/M has comparable hydrolytic ability with the free enzyme. To the best of our knowledge, this is the first report of an immobilization study of an α-amylase from Anoxybacillus spp. and the first report of α-amylase immobilization using ReliZyme and Immobeads as supports. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

▼ Show Figures

Figure 1

20 pages, 5451 KiB

Open AccessReview

(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †

by Angela La Bella¹, Francesca Leonelli²

, Luisa Maria Migneco¹ and Rinaldo Marini Bettolo^1,*

¹ Dipartimento di Chimica, Università degli Studi di Roma “La Sapienza”, P.le Aldo Moro, 5, I-00185 Roma, Italy

² Dipartimento di Biologia Ambientale, Università degli Studi di Roma “La Sapienza”, P.le Aldo Moro, 5, I-00185 Roma, Italy

Molecules 2016, 21(9), 1197; https://doi.org/10.3390/molecules21091197 - 8 Sep 2016

Cited by 11 | Viewed by 7205

Abstract

In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the [...] Read more.

In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)

▼ Show Figures

Figure 1

12 pages, 849 KiB

Open AccessArticle

Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives

by Guan-Nan Liu^1,2, Rong-Hua Luo³, Yu Zhou², Xing-Jie Zhang³, Jian Li², Liu-Meng Yang³, Yong-Tang Zheng^3,*

and Hong Liu^2,*

¹ College of Life Sciences, China Jiliang University, Hangzhou 310018, Zhejiang, China

² CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

³ Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China

Molecules 2016, 21(9), 1198; https://doi.org/10.3390/molecules21091198 - 8 Sep 2016

Cited by 31 | Viewed by 5675

Abstract

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione [...] Read more.

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC₅₀ < 5 μM) and excellent therapeutic index (TI, CC₅₀/EC₅₀ > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents. Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Graphical abstract

14 pages, 3538 KiB

Open AccessArticle

Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone–Amino Acid Derivatives

by Jaime A. Valderrama^1,2,*

, Virginia Delgado³, Sandra Sepúlveda¹, Julio Benites^1,2

, Cristina Theoduloz⁴, Pedro Buc Calderon^1,5 and Giulio G. Muccioli⁶

¹ Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

² Instituto de Ciencias Exactas y Naturales Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

³ Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 26094411, Chile

⁴ Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile

⁵ Research Group of Toxicology and Cancer Biology, Louvain Drug Research Institute, Université Catholique de Louvain, 73 Avenue E. Mounier, GTOX 7309, Brussels 1200, Belgium

⁶ Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, Louvain Drug Research Institute, Université Catholique de Louvain, 72 Avenue E. Mounier, BPBL 7201, Brussels 1200, Belgium

Molecules 2016, 21(9), 1199; https://doi.org/10.3390/molecules21091199 - 8 Sep 2016

Cited by 28 | Viewed by 4747

Abstract

A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium [...] Read more.

A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure–activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC₅₀ ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24). Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Graphical abstract

17 pages, 4577 KiB

Open AccessArticle

LC-MS Supported Studies on the in Vitro Metabolism of both Enantiomers of Flubatine and the in Vivo Metabolism of (+)-[¹⁸F]Flubatine—A Positron Emission Tomography Radioligand for Imaging α4β2 Nicotinic Acetylcholine Receptors

by Friedrich-Alexander Ludwig¹, René Smits², Steffen Fischer¹, Cornelius K. Donat³, Alexander Hoepping², Peter Brust^1,*

and Jörg Steinbach¹

¹ Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, Leipzig 04318, Germany

² ABX Advanced Biochemical Compounds GmbH, Heinrich-Gläser-Straße 10-14, Radeberg 01454, Germany

³ Division of Brain Sciences, Imperial College London, Du Cane Road, London W12 0NN, UK

Molecules 2016, 21(9), 1200; https://doi.org/10.3390/molecules21091200 - 8 Sep 2016

Cited by 9 | Viewed by 6665

Abstract

Both enantiomers of [¹⁸F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo [...] Read more.

Both enantiomers of [¹⁸F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo has been performed. (+)- and (−)-flubatine, respectively, were incubated with liver microsomes from mouse and human in the presence of NADPH (β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt). Phase I in vitro metabolites were detected and their structures elucidated by LC-MS/MS (liquid chromatography-tandem mass spectrometry). Selected metabolite candidates were synthesized and investigated for structural confirmation. Besides a high level of in vitro stability, the microsomal incubations revealed some species differences as well as enantiomer discrimination with regard to the formation of monohydroxylated products, which was identified as the main metabolic pathway in this assay. Furthermore, after injection of 250 MBq (+)-[¹⁸F]flubatine (specific activity > 350 GBq/μmol) into mouse, samples were prepared from brain, liver, plasma, and urine after 30 min and investigated by radio-HPLC (high performance liquid chromatography with radioactivity detection). For structure elucidation of the radiometabolites of (+)-[¹⁸F]flubatine formed in vivo, identical chromatographic conditions were applied to LC-MS/MS and radio-HPLC to compare samples obtained in vitro and in vivo. By this correlation approach, we assigned three of four main in vivo radiometabolites to products that are exclusively C- or N-hydroxylated at the azabicyclic ring system of the parent molecule. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Graphical abstract

15 pages, 1320 KiB

Open AccessArticle

Chemical and Antioxidant Properties of Wild Edible Mushrooms from Native Nothofagus spp. Forest, Argentina

by Carolina V. Toledo¹, Carolina Barroetaveña^1,2,3,*, Ângela Fernandes⁴, Lillian Barros^4,5 and Isabel C. F. R. Ferreira^4,*

¹ Centro de Investigación y Extensión Forestal Andino Patagónico (CIEFAP), Ruta 259, Km 4, Esquel 9200, Chubut, Argentina

² Facultad de Ingeniería, Universidad Nacional de la Patagonia S.J. Bosco, Ruta 259, Km 4, Esquel 9200, Chubut, Argentina

³ Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Av. Rivadavia 1917, C1033AAJ, CABA, Argentina

⁴ MountainResearch Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Bragança, Portugal

⁵ Laboratory of Separation and Reaction Engineering–Laboratory of Catalysis and Materials (LSRE-LCM), Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1134, 5301-857 Bragança, Portugal

Molecules 2016, 21(9), 1201; https://doi.org/10.3390/molecules21091201 - 8 Sep 2016

Cited by 55 | Viewed by 10994

Abstract

This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied [...] Read more.

This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied between 3.35 g/100 g dw in Cyttaria hariotii and 22.29 g/100 g dw in Lepista nuda. All of them presented mannitol and trehalose as main sugars. Mannitol was significantly higher in Ramaria patagonica, although absent in Fistulina endoxantha, whereas trehalose predominated in Aleurodiscus vitellinus, Hydropus dusenii, Cortinarius magellanicus, C. hariotii, Grifola gargal and L. nuda, ranging from 1.15 to 10.26 g/100 g dw; it was absent in R. patagonica. The major fatty acid found was linoleic acid, followed by oleic acid and palmitic acid. All species presented oxalic and fumaric acids, while some also had malic, quinic and citric acids. Tocopherols composition was variable. Cortinarius magellanicus presented significantly higher contents of both α-tocopherol and β-tocopherol. R. patagonica presented the best results in all the antioxidant activity assays (EC₅₀ values ≤ 1 mg/mL) and the highest content of phenolic compounds presenting gallic, p-hydroxybenzoic, p-coumaric and cinnamic acids. This study constitutes the first report on chemical composition and nutritional value of most of these edible mushroom species. Furthermore, it provides important information necessary to characterize and define the use of these species as gastronomic delicacies, functional foods and sources of bioactive compounds. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Graphical abstract

13 pages, 387 KiB

Open AccessArticle

Characterization of French Coriander Oil as Source of Petroselinic Acid

by Evelien Uitterhaegen^1,2,3,†, Klicia A. Sampaio^3,4,†, Elisabeth I. P. Delbeke³, Wim De Greyt⁵, Muriel Cerny^1,2, Philippe Evon^1,2

, Othmane Merah^1,2

, Thierry Talou^1,2 and Christian V. Stevens^3,*

¹ Laboratoire de Chimie Agro-Industrielle, Université de Toulouse, INP, ENSIACET, 4 Allée Emile Monso, BP 44362, 31030 Toulouse Cedex 4, France

² Laboratoire de Chimie Agro-Industrielle, Institut National de la Recherche Agronomique, 31030 Toulouse Cedex 4, France

³ SynBioC, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium

⁴ EXTRAE, Food Engineering Department, University of Campinas, Rua Monteiro Lobato, 80, 13083-862 Campinas-São Paulo, Brazil

⁵ Desmet-Ballestra Group, Corporate Village, Da Vincilaan 2, 1935 Zaventem, Belgium

Molecules 2016, 21(9), 1202; https://doi.org/10.3390/molecules21091202 - 8 Sep 2016

Cited by 57 | Viewed by 9767

Abstract

Coriander vegetable oil was extracted from fruits of French origin in a 23% yield. The oil was of good quality, with a low amount of free fatty acids (1.8%) and a concurrently high amount of triacylglycerols (98%). It is a rich source of [...] Read more.

Coriander vegetable oil was extracted from fruits of French origin in a 23% yield. The oil was of good quality, with a low amount of free fatty acids (1.8%) and a concurrently high amount of triacylglycerols (98%). It is a rich source of petroselinic acid (C18:1n-12), an important renewable building block, making up 73% of all fatty acids, with also significant amounts of linoleic acid (14%), oleic acid (6%), and palmitic acid (3%). The oil was characterized by a high unsaponifiable fraction, comprising a substantial amount of phytosterols (6.70 g/kg). The main sterol markers were β-sitosterol (35% of total sterols), stigmasterol (24%), and Δ⁷-stigmastenol (18%). Squalene was detected at an amount of 0.2 g/kg. A considerable amount of tocols were identified (500 mg/kg) and consisted mainly of tocotrienols, with γ-tocotrienol as the major compound. The phospholipid content was low at 0.3%, of which the main phospholipid classes were phosphatidic acid (33%), phosphatidylcholine (25%), phosphatidylinositol (17%), and phosphatidylethanolamine (17%). About 50% of all phospholipids were non-hydratable. The β-carotene content was low at 10 mg/kg, while a significant amount of chlorophyll was detected at about 11 mg/kg. An iron content of 1.4 mg/kg was determined through element analysis of the vegetable oil. The influence of fruit origin on the vegetable oil composition was shown to be very important, particularly in terms of the phospholipids, sterols, and tocols composition. Full article

(This article belongs to the Special Issue Chemicals from Biomass)

▼ Show Figures

Graphical abstract

15 pages, 899 KiB

Open AccessArticle

Improvement in Flavonoids and Phenolic Acids Production and Pharmaceutical Quality of Sweet Basil (Ocimum basilicum L.) by Ultraviolet-B Irradiation

by Ali Ghasemzadeh^1,*, Sadegh Ashkani², Ali Baghdadi¹

, Alireza Pazoki², Hawa Z. E. Jaafar¹ and Asmah Rahmat³

¹ Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Department of Agronomy and Plant Breeding, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Islamic Azad University, Tehran, Iran

³ Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Molecules 2016, 21(9), 1203; https://doi.org/10.3390/molecules21091203 - 9 Sep 2016

Cited by 97 | Viewed by 10231

Abstract

Sweet basil (Ocimum basilicum Linnaeus) is aromatic herb that has been utilized in traditional medicine. To improve the phytochemical constituents and pharmaceutical quality of sweet basil leaves, ultraviolet (UV)-B irradiation at different intensities (2.30, 3.60, and 4.80 W/m²) and durations [...] Read more.

Sweet basil (Ocimum basilicum Linnaeus) is aromatic herb that has been utilized in traditional medicine. To improve the phytochemical constituents and pharmaceutical quality of sweet basil leaves, ultraviolet (UV)-B irradiation at different intensities (2.30, 3.60, and 4.80 W/m²) and durations (4, 6, 8, and 10-h) was applied at the post-harvest stage. Total flavonoid content (TFC) and total phenolic content (TPC) were measured using spectrophotometric method, and individual flavonoids and phenolic acids were identified using ultra-high performance liquid chromatography. As a key enzyme for the metabolism of flavonoids, chalcone synthase (CHS) activity, was measured using a CHS assay. Antioxidant activity and antiproliferative activity of extracts against a breast cancer cell line (MCF-7) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, respectively. UV-B irradiation at an intensity of 3.60 W/m² increased TFC approximately 0.85-fold and also increased quercetin (0.41-fold), catechin (0.85-fold), kaempferol (0.65-fold) rutin (0.68-fold) and luteolin (1.00-fold) content. The highest TPC and individual phenolic acid (gallic acid, cinnamic acid and ferulic acid) was observed in the 3.60 W/m² of UV-B treatment. Cinnamic acid and luteolin were not detected in the control plants, production being induced by UV-B irradiation. Production of these secondary metabolites was also significantly influenced by the duration of UV-B irradiation. Irradiation for 8-h led to higher TFC, TPC and individual flavonoids and phenolic acids than for the other durations (4, 8, and 10-h) except for cinnamic acid, which was detected at higher concentration when irradiated for 6-h. Irradiation for 10-h significantly decreased the secondary metabolite production in sweet basil leaves. CHS activity was induced by UV-B irradiation and highest activity was observed at 3.60 W/m² of UV-B irradiation. UV-B treated leaves presented the highest DPPH activity and antiproliferative activity with a half-maximal inhibitory concentration (IC₅₀) value of 56.0 and 40.8 µg/mL, respectively, over that of the control plants (78.0 and 58.2 µg/mL, respectively). These observations suggest that post-harvest irradiation with UV-B can be considered a promising technique to improve the healthy–nutritional and pharmaceutical properties of sweet basil leaves. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

21 pages, 1450 KiB

Open AccessArticle

Chemical Analysis of Dietary Constituents in Rosa roxburghii and Rosa sterilis Fruits

by Meng-Hua Liu¹, Qi Zhang¹, Yuan-He Zhang², Xian-Yuan Lu¹, Wei-Ming Fu^1,2,* and Jing-Yu He^2,*

¹ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China

² Bioengineering Research Centre, Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, Guangdong, China

Molecules 2016, 21(9), 1204; https://doi.org/10.3390/molecules21091204 - 9 Sep 2016

Cited by 114 | Viewed by 11698

Abstract

Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R. [...] Read more.

Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R. sterilis fruits, the essential oils and constituents in a methanol extract have been analyzed and compared by GC-MS and UFLC/Q-TOF-MS, respectively. As a result, a total of 135 volatile compounds were identified by GC-MS and 91 components were different between R. roxburghii and R. sterilis fruits; a total of 59 compounds in methanol extracts were identified by UFLC/Q-TOF-MS, including 13 organic acids, 12 flavonoids, 11 triterpenes, nine amino acids, five phenylpropanoid derivatives, four condensed tannins, two stilbenes, two benzaldehyde derivatives and one benzoic acid derivative; and nine characteristic compounds were found between R. roxburghii and R. sterilis fruits. This systematic study plays an important role for R. roxburghii and R. sterilis fruits in the product development. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

12 pages, 542 KiB

Open AccessArticle

A Highly Efficient and Reusable Palladium(II)/Cationic 2,2’-Bipyridyl-Catalyzed Stille Coupling in Water

by Wei-Yi Wu^†, Ling-Jun Liu, Fen-Ping Chang, Yu-Lun Cheng and Fu-Yu Tsai^*

Institute of Organic and Polymeric Materials, National Taipei University of Technology, 1, Sec. 3, Chung-Hsiao E. Rd., Taipei 10608, Taiwan

Molecules 2016, 21(9), 1205; https://doi.org/10.3390/molecules21091205 - 9 Sep 2016

Cited by 8 | Viewed by 6698

Abstract

A water-soluble PdCl₂(NH₃)₂/cationic 2,2′-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in [...] Read more.

A water-soluble PdCl₂(NH₃)₂/cationic 2,2′-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in the presence of NaHCO₃ as a base to afford corresponding Stille coupling products in good to high yields. When aryltributylstannanes were employed, the reactions proceeded smoothly under a very low catalyst loading (as little as 0.0001 mol %). After simple extraction, the residual aqueous phase could be reused in subsequent runs, making this Stille coupling economical. In the case of tetramethylstannane, however, a greater catalyst loading (1 mol %) and the use of tetraethylammonium iodide as a phase-transfer agent were required in order to obtain satisfactory yields. Full article

(This article belongs to the Special Issue Palladium Catalysts 2016)

▼ Show Figures

Graphical abstract

13 pages, 3254 KiB

Open AccessArticle

Anti-Inflammatory Effects and Mechanisms of Action of Coussaric and Betulinic Acids Isolated from Diospyros kaki in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

by Kyoung-Su Kim^1,†, Dong-Sung Lee^2,†, Dong-Cheol Kim³, Chi-Su Yoon³, Wonmin Ko³, Hyuncheol Oh³ and Youn-Chul Kim^3,*

¹ Research Institute of Pharmaceutical Sciences, Keimyung University, 1095 Dalgubeol-Daero, Daegu 42601, Korea

² College of Pharmacy, Chosun University, Dong-Gu, Gwangju 61452, Korea

³ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea

Molecules 2016, 21(9), 1206; https://doi.org/10.3390/molecules21091206 - 9 Sep 2016

Cited by 54 | Viewed by 9278

Abstract

Diospyros kaki Thunb. is widely distributed in East Asian countries, its leaves being mainly used for making tea. In this study, coussaric acid (CA) and betulinic acid (BA), both triterpenoid compounds, were obtained from D. kaki leaf extracts through bioassay-guided isolation. CA and [...] Read more.

Diospyros kaki Thunb. is widely distributed in East Asian countries, its leaves being mainly used for making tea. In this study, coussaric acid (CA) and betulinic acid (BA), both triterpenoid compounds, were obtained from D. kaki leaf extracts through bioassay-guided isolation. CA and BA showed anti-inflammatory effects via inhibition of the nuclear factor-κB (NF-κB) pathway, providing important information on their anti-inflammatory mechanism. Furthermore, they markedly inhibited nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and suppressed tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels. Furthermore, they decreased protein expression of inducible nitric oxide synthase and cyclooxygenase-2. Pre-treatment with CA and BA inhibited LPS-induced NF-κB. We further examined the effects of CA and BA on heme oxygenase (HO)-1 expression in RAW 264.7 macrophages: BA induced HO-1 protein expression in a dose-dependent manner, while CA had no effect. We also investigated whether BA treatment induced nuclear translocation of Nrf2. BA inhibited LPS-induced NF-κB-binding activity, as well as pro-inflammatory mediator and cytokine production (e.g., NO, PGE₂, TNF-α, IL-1β, IL-6), by partial reversal of this effect by SnPP, an inhibitor of HO-1. These findings further elucidate the anti-inflammatory mechanism of CA and BA isolated from D. kaki. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

▼ Show Figures

Figure 1

9 pages, 539 KiB

Open AccessArticle

Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives

by Shaojun Zheng^1,2,3, Xinping Zhou², Shixun Xu², Rui Zhu¹, Hongjin Bai^2,* and Jiwen Zhang^2,3,*

¹ School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, China

² Key Laboratory of Protection & Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps/College of Life Sciences, Tarim University, Alar 843300, Xinjiang, China

³ Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Yangling 712100, Shaanxi, China

Molecules 2016, 21(9), 1207; https://doi.org/10.3390/molecules21091207 - 9 Sep 2016

Cited by 15 | Viewed by 5128

Abstract

A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed [...] Read more.

A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R₄ and R₅ significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents. Full article

(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)

▼ Show Figures

Graphical abstract

18 pages, 9282 KiB

Open AccessArticle

Impact of Biohybrid Magnetite Nanoparticles and Moroccan Propolis on Adherence of Methicillin Resistant Strains of Staphylococcus aureus

by Soukaina El-Guendouz^1,2, Smail Aazza^1,2, Badiaa Lyoussi¹, Vassya Bankova³

, João P. Lourenço^4,5, Ana M. Rosa Costa⁴

, José F. Mariano⁶

, Maria G. Miguel^2,*

and Maria L. Faleiro⁷

¹ Laboratory of Physiology-Pharmacology-Environmental Health, Faculty of Sciences Dhar El Mehraz, BP 1796 Atlas, University Sidi Mohamed Ben Abdallah, Fez 30 000, Morocco

² Department of Chemistry and Pharmacy, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, MeditBio, Faro 8005-139, Portugal

³ Institute of Organic Chemistry with Centre of Phytochemistry, Acad. G. Bonchev strl. bl. 9, Sofia 1113, Bulgaria

⁴ Algarve Chemistry Research Centre(CIQA) and Department of Chemistry and Pharmacy, Faculty of Science and Technology, University of Algarve, Faro 8005-139, Portugal

⁵ CQE, Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, Lisboa 1049-001, Portugal

⁶ Department of Physics and CeFEMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, Faro 8005-139, Portugal

⁷ Department of Biological Sciences and Bioengineering, Faculty of Science and Technology, University of Algarve, Center for Biomedical Research, Faro 8005-139, Portugal

Molecules 2016, 21(9), 1208; https://doi.org/10.3390/molecules21091208 - 9 Sep 2016

Cited by 28 | Viewed by 6890

Abstract

Biofilm bacteria are more resistant to antibiotics than planktonic cells. Propolis possesses antimicrobial activity. Generally, nanoparticles containing heavy metals possess antimicrobial and antibiofilm properties. In this study, the ability of adherence of Methicillin Resistant Strains of Staphylococcus aureus (MRSA) to catheters treated with [...] Read more.

Biofilm bacteria are more resistant to antibiotics than planktonic cells. Propolis possesses antimicrobial activity. Generally, nanoparticles containing heavy metals possess antimicrobial and antibiofilm properties. In this study, the ability of adherence of Methicillin Resistant Strains of Staphylococcus aureus (MRSA) to catheters treated with magnetite nanoparticles (MNPs), produced by three methods and functionalized with oleic acid and a hydro-alcoholic extract of propolis from Morocco, was evaluated. The chemical composition of propolis was established by gas chromatography mass spectrometry (GC-MS), and the fabricated nanostructures characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Mossbauer spectroscopy and Fourrier transform infrared spectroscopy (FTIR). The capacity for impairing biofilm formation was dependent on the strain, as well as on the mode of production of MNPs. The co-precipitation method of MNPs fabrication using Fe³⁺ and Na₂SO₃ solution and functionalized with oleic acid and propolis was the most effective in the impairment of adherence of all MRSA strains to catheters (p < 0.001). The adherence of the strain MRSA16 was also significantly lower (p < 0.001) when the catheters were treated with the hybrid MNPs with oleic acid produced by a hydrothermal method. The anti-MRSA observed can be attributed to the presence of benzyl caffeate, pinocembrin, galangin, and isocupressic acid in propolis extract, along with MNPs. However, for MRSA16, the impairment of its adherence on catheters may only be attributed to the hybrid MNPs with oleic acid, since very small amount, if any at all of propolis compounds were added to the MNPs. Full article

▼ Show Figures

Figure 1

26 pages, 4284 KiB

Open AccessArticle

Detection of 191 Taxifolin Metabolites and Their Distribution in Rats Using HPLC-ESI-IT-TOF-MSⁿ

by Ping Yang, Feng Xu^*, Hong-Fu Li, Yi Wang, Feng-Chun Li, Ming-Ying Shang, Guang-Xue Liu, Xuan Wang and Shao-Qing Cai^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Molecules 2016, 21(9), 1209; https://doi.org/10.3390/molecules21091209 - 13 Sep 2016

Cited by 84 | Viewed by 8649

Abstract

Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSⁿ method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites [...] Read more.

Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSⁿ method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives. Full article

(This article belongs to the Section Metabolites)

▼ Show Figures

Graphical abstract

12 pages, 2390 KiB

Open AccessArticle

Novel Enantiopure Sigma Receptor Modulators: Quick (Semi-)Preparative Chiral Resolution via HPLC and Absolute Configuration Assignment

by Marta Rui^1,2, Annamaria Marra¹, Vittorio Pace², Markus Juza³, Daniela Rossi¹ and Simona Collina^1,*

¹ Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, Pavia 27100, Italy

² Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, Vienna 1090, Austria

³ Corden Pharma Switzerland LLC, Eichenweg 1, Liestal 4410, Switzerland

Molecules 2016, 21(9), 1210; https://doi.org/10.3390/molecules21091210 - 10 Sep 2016

Cited by 8 | Viewed by 5524

Abstract

The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here, we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine [...] Read more.

The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here, we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All of the studied compounds have been prepared both in racemic and enantiomerically-pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up. A systematic analytical screening, involving several combinations of chiral stationary and mobile phases, allowed us to optimize the analytical resolution and to set up the (semi-)preparative chromatographic conditions. Applying the optimized procedure, the enantiomeric resolution of the studied compounds was successfully achieved, obtaining all of the compounds with an enantiomeric excess higher than 95%. Lastly, the absolute configuration has been empirically assigned to enantiopure compounds, combining the electronic circular dichroism (ECD) technique to the elution order study. Full article

(This article belongs to the Special Issue Chiral Drugs)

▼ Show Figures

Graphical abstract

11 pages, 1682 KiB

Open AccessArticle

Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria

by Malena E. Skogman¹, Sonja Kanerva¹, Suvi Manner², Pia M. Vuorela¹ and Adyary Fallarero^1,*

¹ Pharmaceutical Design and Discovery Group (PharmDD), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, FI-00014 Helsinki, Finland

² Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, BioCity, Artillerigatan 6 A, FI-20520 Turku, Finland

Molecules 2016, 21(9), 1211; https://doi.org/10.3390/molecules21091211 - 10 Sep 2016

Cited by 48 | Viewed by 13507

Abstract

Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors [...] Read more.

Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors from natural compound libraries. In this system, QS is correlated with the production of violacein, which is directly controlled by the LuxI/LuxR system in Chromobacterium violaceum ATCC 31532. The parallel use of C. violaceum Tn5-mutant CV026, which depends on auto-inducer addition, allows simultaneous discrimination of compounds that act as quenchers of the AHL signal (quorum quenchers). The incorporation of a redox stain into the platform allowed further distinction between QS inhibitors, quorum quenchers and antibacterial compounds. A pilot screening was performed with 465 natural and synthetic flavonoids. All the most active compounds were flavones and they displayed potencies (IC₅₀) in the range of 3.69 to 23.35 μM. These leads were particularly promising as they inhibited the transition from microcolonies into mature biofilms from Escherichia coli and Pseudomonas aeruginosa strains. This approach can be very effective in identifying new antimicrobials posing lesser risks of resistance. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Graphical abstract

16 pages, 2934 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates

by Brigitta Bodnár¹, Erzsébet Mernyák², János Wölfling², Gyula Schneider², Bianka Edina Herman³, Mihály Szécsi³, Izabella Sinka⁴, István Zupkó⁴

, Zoltán Kupihár^1,* and Lajos Kovács^1,*

¹ Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary

² Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary

³ 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary

⁴ Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary

Molecules 2016, 21(9), 1212; https://doi.org/10.3390/molecules21091212 - 10 Sep 2016

Cited by 18 | Viewed by 7826

Abstract

2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields [...] Read more.

2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3′-hydroxy groups of the nucleosides were protected by acetyl groups and the 5′-hydroxy groups were modified by the tosyl–azide exchange method. The commonly used conditions for click reaction between the protected-5′-azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC₅₀ value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC₅₀ = 19 μM). Full article

(This article belongs to the Collection New Frontiers in Nucleic Acid Chemistry)

▼ Show Figures

Graphical abstract

14 pages, 7494 KiB

Open AccessArticle

Antiinflammatory and Antiphotodamaging Effects of Ergostatrien-3β-ol, Isolated from Antrodia camphorata, on Hairless Mouse Skin

by Yueh-Hsiung Kuo^1,2

, Tzu-Yu Lin³, Ya-Jhen You³, Kuo-Ching Wen³, Ping-Jyun Sung⁴

and Hsiu-Mei Chiang^3,*

¹ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

² Department of Biotechnology, Asia University, Taichung 413, Taiwan

³ Department of Cosmeceutics, China Medical University, Taichung 404, Taiwan

⁴ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

Molecules 2016, 21(9), 1213; https://doi.org/10.3390/molecules21091213 - 10 Sep 2016

Cited by 30 | Viewed by 7929

Abstract

Ergostatrien-3β-ol (EK100), isolated from the submerged whole broth of Antrodia camphorata, has antidiabetic, hyperlipidemic, and hepatoprotective activities. However, the antiphotodamage activity of EK100 has still not been revealed. Inflammation and collagen degradation contribute to skin photodamage and premature aging. In the present [...] Read more.

Ergostatrien-3β-ol (EK100), isolated from the submerged whole broth of Antrodia camphorata, has antidiabetic, hyperlipidemic, and hepatoprotective activities. However, the antiphotodamage activity of EK100 has still not been revealed. Inflammation and collagen degradation contribute to skin photodamage and premature aging. In the present study, in vivo experiments were designed to investigate the antiinflammatory and antiphotodamaging activities of EK100 in hairless mice by physiological and histological analysis of the skin. Results indicated that topical application of EK100 (25 and 100 μM) for 10 weeks efficiently inhibited ultraviolet B (UVB)-induced wrinkle formation, erythema, and epidermal thickness in the mice skin. EK100 also restored UVB-induced collagen content reduction in hairless mice skin. In addition, the immunohistochemistry results indicated that EK100 significantly inhibited the UVB-induced expression of matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and nuclear factor kappaB (NF-κB) in the mouse skin. The expression of these proteins was similar to the Normal group after 100 μM EK100 treatment. EK100 inhibited collagen degradation in the skin through MMP-1 inhibition and antiinflammation. EK100 significantly reduced the transepidermal water loss (TEWL), indicating that EK100 protected skin from UVB-induced damage. Our findings strongly suggest that EK100 has significant beneficial antiinflammatory and antiphotoaging activities and that EK100 can be developed as an antiphotodamaging agent. Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Figure 1

17 pages, 1224 KiB

Open AccessArticle

Formation of Hydrogen Sulfide in Wine: Interactions between Copper and Sulfur Dioxide

by Marlize Z. Bekker^*, Mark E. Smith, Paul A. Smith and Eric N. Wilkes

The Australian Wine Research Institute, P.O. Box 197, Glen Osmond, 5064 South Australia, Australia

Molecules 2016, 21(9), 1214; https://doi.org/10.3390/molecules21091214 - 10 Sep 2016

Cited by 35 | Viewed by 11198

Abstract

The combined synergistic effects of copper (Cu²⁺) and sulfur dioxide (SO₂) on the formation of hydrogen sulfide (H₂S) in Verdelho and Shiraz wine samples post-bottling was studied over a 12-month period. The combined treatment of Cu²⁺ [...] Read more.

The combined synergistic effects of copper (Cu²⁺) and sulfur dioxide (SO₂) on the formation of hydrogen sulfide (H₂S) in Verdelho and Shiraz wine samples post-bottling was studied over a 12-month period. The combined treatment of Cu²⁺ and SO₂ significantly increased H₂S formation in Verdelho wines samples that were not previously treated with either Cu²⁺ or SO₂. The formation of H₂S produced through Cu²⁺ mediated reactions was likely either: (a) directly through the interaction of SO₂ with either Cu²⁺ or H₂S; or (b) indirectly through the interaction of SO₂ with other wine matrix compounds. To gain better understanding of the mechanisms responsible for the significant increases in H₂S concentration in the Verdelho samples, the interaction between Cu²⁺ and SO₂ was studied in a model wine matrix with and without the presence of a representative thiol quenching compound (4-methylbenzoquinone, 4MBQ). In these model studies, the importance of naturally occurring wine compounds and wine additives, such as quinones, SO₂, and metal ions, in modulating the formation of H₂S post-bottling was demonstrated. When present in equimolar concentrations a 1:1 ratio of H₂S- and SO₂-catechol adducts were produced. At wine relevant concentrations, however, only SO₂-adducts were produced, reinforcing that the competition reactions of sulfur nucleophiles, such as H₂S and SO₂, with wine matrix compounds play a critical role in modulating final H₂S concentrations in wines. Full article

(This article belongs to the Collection Wine Chemistry)

▼ Show Figures

Graphical abstract

13 pages, 2321 KiB

Open AccessArticle

Enhancing the Antioxidant Ability of Trametes versicolor Polysaccharopeptides by an Enzymatic Hydrolysis Process

by Mei-Hsin Jhan¹, Ching-Hua Yeh¹, Chia-Chun Tsai¹, Ching-Tian Kao², Chao-Kai Chang³

and Chang-Wei Hsieh^1,2,*

¹ Department of Medicinal Botanicals and Health Applications, Da-Yeh University, No.168, Xuefu Rd., Dacun Township, Chang-Hua 51591, Taiwan

² Department of Pediatrics, Cheng Ching General Hospital, Taichung 400, Taiwan

³ Biotechnology Research Center, Da-Yeh University, 168 University Rd, Dacun, Chang-Hua 51591, Taiwan

Molecules 2016, 21(9), 1215; https://doi.org/10.3390/molecules21091215 - 10 Sep 2016

Cited by 21 | Viewed by 5755

Abstract

Polysaccharopeptides (PSPs) are among the main bioactive constituents of Trametes versicolor (T. versicolor). The purpose of this research was to investigate the antioxidant activities of enzymatic hydrolysates obtained from T. versicolor polysaccharopeptides by 80 U/mL β-1,3-glucanase (PSPs-EH80). The half-inhibitory concentration (IC₅₀ [...] Read more.

Polysaccharopeptides (PSPs) are among the main bioactive constituents of Trametes versicolor (T. versicolor). The purpose of this research was to investigate the antioxidant activities of enzymatic hydrolysates obtained from T. versicolor polysaccharopeptides by 80 U/mL β-1,3-glucanase (PSPs-EH80). The half-inhibitory concentration (IC₅₀) of PSPs-EH80 in metal chelating assay, ABTS and DPPH radical scavenging test results were 0.83 mg/mL, 0.14 mg/mL and 0.52 mg/mL, respectively, which were lower than that of PSPs-EH 20 U/mL. The molecular weights of the PSPs-EH80 hydrolysates were 300, 190, 140 and 50 kDa, respectively, and the hydrolysis of polysaccharides by β-1,3-glucanase did not change the original functional group. PSPs-EH80 reduced the reactive oxygen species (ROS) content at least twice that of treatment without PSPs-EH80. In addition, an oxidative damage test showed that PSPs-EH80 can improve HaCaT cell survival. According to our results, PSP demonstrates the potential of anti-oxidative damage; besides, enzyme hydrolysis can improve the ability of the PSP. Full article

▼ Show Figures

Figure 1

22 pages, 1545 KiB

Open AccessFeature PaperReview

Insoluble-Bound Phenolics in Food

by Fereidoon Shahidi^*

and JuDong Yeo

Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, Canada

Molecules 2016, 21(9), 1216; https://doi.org/10.3390/molecules21091216 - 11 Sep 2016

Cited by 399 | Viewed by 17131

Abstract

This contribution provides a review of the topic of insoluble-bound phenolics, especially their localization, synthesis, transfer and formation in plant cells, as well as their metabolism in the human digestive system and corresponding bioactivities. In addition, their release from the food matrix during [...] Read more.

This contribution provides a review of the topic of insoluble-bound phenolics, especially their localization, synthesis, transfer and formation in plant cells, as well as their metabolism in the human digestive system and corresponding bioactivities. In addition, their release from the food matrix during food processing and extraction methods are discussed. The synthesis of phenolics takes place mainly at the endoplasmic reticulum and they are then transferred to each organ through transport proteins such as the ATP-binding cassette (ABC) and multidrug and toxic compound extrusion (MATE) transporter at the organ’s compartment membrane or via transport vesicles such as cytoplasmic and Golgi vesicles, leading to the formation of soluble and insoluble-bound phenolics at the vacuole and cell wall matrix, respectively. This part has not been adequately discussed in the food science literature, especially regarding the synthesis site and their transfer at the cellular level, thus this contribution provides valuable information to the involved scientists. The bound phenolics cannot be absorbed at the small intestine as the soluble phenolics do (5%–10%), thus passing into the large intestine and undergoing fermentation by a number of microorganisms, partially released from cell wall matrix of foods. Bound phenolics such as phenolic acids and flavonoids display strong bioactivities such as anticancer, anti-inflammation and cardiovascular disease ameliorating effects. They can be extracted by several methods such as acid, alkali and enzymatic hydrolysis to quantify their contents in foods. In addition, they can also be released from the cell wall matrix during food processing procedures such as fermentation, germination, roasting, extrusion cooking and boiling. This review provides critical information for better understanding the insoluble-bound phenolics in food and fills an existing gap in the literature. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

▼ Show Figures

Figure 1

12 pages, 1449 KiB

Open AccessCommunication

A Selective Cyclic Peptidic Human SIRT5 Inhibitor

by Jiajia Liu, Yajun Huang and Weiping Zheng^*

School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, China

Molecules 2016, 21(9), 1217; https://doi.org/10.3390/molecules21091217 - 10 Sep 2016

Cited by 17 | Viewed by 5883

Abstract

In the current study, we discovered that a side chain-to-side chain cyclic pentapeptide harboring a central N^ε-carboxyethyl-thiocarbamoyl-lysine residue behaved as a strong and selective (versus human SIRT1/2/3/6) inhibitor against human SIRT5-catalyzed deacylation reaction. This compound was also found to be proteolytically [...] Read more.

In the current study, we discovered that a side chain-to-side chain cyclic pentapeptide harboring a central N^ε-carboxyethyl-thiocarbamoyl-lysine residue behaved as a strong and selective (versus human SIRT1/2/3/6) inhibitor against human SIRT5-catalyzed deacylation reaction. This compound was also found to be proteolytically much more stable than its linear counterpart. This compound could be a valuable lead for developing stronger, selective, metabolically stable, and cell permeable human SIRT5 inhibitors. Full article

▼ Show Figures

Graphical abstract

13 pages, 8404 KiB

Open AccessArticle

Evaluation of PVP/Au Nanocomposite Fibers as Heterogeneous Catalysts in Indole Synthesis

by Ioanna Savva^1,*, Andreas S. Kalogirou², Mariliz Achilleos¹, Eugenia Vasile³, Panayiotis A. Koutentis²

and Theodora Krasia-Christoforou^1,*

¹ Department of Mechanical and Manufacturing Engineering, University of Cyprus, P. O. Box 20537, 1678 Nicosia, Cyprus

² Department of Chemistry, University of Cyprus, P. O. Box 20537, 1678 Nicosia, Cyprus

³ Department of Physics, Politehnica University of Bucharest, 313 Splaiul Independentei, Bucharest 060042, Romania

Molecules 2016, 21(9), 1218; https://doi.org/10.3390/molecules21091218 - 10 Sep 2016

Cited by 18 | Viewed by 9079

Abstract

Electrospun nanocomposite fibers consisting of crosslinked polyvinylpyrrolidone (PVP) chains and gold nanoparticles (Au NPs) were fabricated, starting from highly stable PVP/Au NP colloidal solutions with different NP loadings, followed by thermal treatment. Information on the morphological characteristics of the fibers and of the [...] Read more.

Electrospun nanocomposite fibers consisting of crosslinked polyvinylpyrrolidone (PVP) chains and gold nanoparticles (Au NPs) were fabricated, starting from highly stable PVP/Au NP colloidal solutions with different NP loadings, followed by thermal treatment. Information on the morphological characteristics of the fibers and of the embedded Au NPs was obtained by electron microscopy. Cylindrical, bead-free fibers were visualized by Scanning Electron Microscopy (SEM) while Transmission Electron Microscopy (TEM) and Energy Diffraction X-ray (EDX) analysis supported the presence of Au NPs within the fibers and gave information on their morphologies and average diameters. These materials were briefly evaluated as heterogeneous catalytic supports for the gold-catalyzed intramolecular cyclisation of 2‑(phenylethynyl)aniline to form 2-phenyl-1H-indole. The performance of the gold catalyst was strongly dependent on the Au NP size, with the system containing the smallest Au NPs being the more effective. Moreover, a slight drop of their catalytic efficiency was observed after three consecutive reaction runs, which was attributed to morphological changes as a consequence of fiber merging. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

▼ Show Figures

Figure 1

12 pages, 1945 KiB

Open AccessArticle

Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading

by Yang Qiao^1,†, Huan He^2,†, Zeyu Zhang², Zhangping Liao², Dong Yin³, Dan Liu^2,*, Bo Yi^4,* and Ming He^1,*

¹ Jiangxi Provincial Institute of Hypertension, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China

² Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China

³ Jiangxi Provincial Key Laboratory of Molecular Medicine at the Second Affiliated Hospital, Nanchang University, Nanchang 330006, China

⁴ Second Abdominal Surgery Department, Jiangxi Province Tumor Hospital, Nanchang 330029, China

Molecules 2016, 21(9), 1219; https://doi.org/10.3390/molecules21091219 - 16 Sep 2016

Cited by 22 | Viewed by 5874

Abstract

Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect [...] Read more.

Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU), and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

13 pages, 2974 KiB

Open AccessArticle

Synthesis of High-Molecular-Weight Multifunctional Glycerol Polyhydroxyurethanes PHUs

by Bassam Nohra¹, Laure Candy¹, Jean-François Blanco², Yann Raoul³ and Zéphirin Mouloungui^1,*

¹ Laboratoire de Chimie Agro-industrielle (LCA), Université de Toulouse, INRA, INPT, Toulouse, France

² Laboratoire de Génie Chimique, Université de Toulouse, CNRS, INPT, UPS, Toulouse, France

³ Oléon SAS, Venette-BP2069-60206 Compiègne CEDEX, France

Molecules 2016, 21(9), 1220; https://doi.org/10.3390/molecules21091220 - 11 Sep 2016

Cited by 12 | Viewed by 8969

Abstract

Glycerol carbonate acrylate is a 5-membered cyclic carbonate synthesized from glycerol that is used as a chemical coupling agent and has proven highly suitable for use in the synthesis of multifunctional polyhydroxyurethanes (PHUs). The multifunctionality of the structure of PHUs is determined by [...] Read more.

Glycerol carbonate acrylate is a 5-membered cyclic carbonate synthesized from glycerol that is used as a chemical coupling agent and has proven highly suitable for use in the synthesis of multifunctional polyhydroxyurethanes (PHUs). The multifunctionality of the structure of PHUs is determined by the density of the carbon-amine groups generated by the Aza-Michael reaction and that of the urethane groups and adjacent primary and secondary hydroxyl groups generated by aminolysis. Glycerol carbonate acrylate is polymerized with polyfunctional mono-, di-, tri, and tetra-amines, by type-AB polyaddition, either in bulk or in solution, through stepwise or one-pot reaction strategies in the absence of added catalysts. These approaches result in the generation of linear, interchain, and crosslinked structures, through the polyaddition of linear and branched amines to the ethylene and cyclic carbonate sites of glycerol carbonate acrylate. The resulting collection of organic molecules gives rise to polyethylene amino ester PHUs with a high molar mass, exceeding 20,000 g·mol⁻¹, with uniform dispersity. Full article

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

▼ Show Figures

Graphical abstract

10 pages, 2703 KiB

Open AccessArticle

Suitable DNA Barcoding for Identification and Supervision of Piper kadsura in Chinese Medicine Markets

by Ning Yu^1,2,†, Hong Gu^1,2,†, Yulong Wei^1,2,†, Ning Zhu^1,2, Yanli Wang^1,2, Haiping Zhang^1,2, Yue Zhu^1,2, Xin Zhang^1,2, Chao Ma^1,2,* and Aidong Sun^1,2,*

¹ College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

² Beijing Key Laboratory of Forest Food Processing and Safety, Beijing Forestry University, Beijing 100083, China

Molecules 2016, 21(9), 1221; https://doi.org/10.3390/molecules21091221 - 12 Sep 2016

Cited by 18 | Viewed by 8140

Abstract

Piper kadsura is a vine-like medicinal plant which is widely used in clinical treatment. However, P. kadsura is often substituted by other materials in the markets, thereby causing health risks. In this study, 38 P. kadsura samples and eight sequences from GenBank, including [...] Read more.

Piper kadsura is a vine-like medicinal plant which is widely used in clinical treatment. However, P. kadsura is often substituted by other materials in the markets, thereby causing health risks. In this study, 38 P. kadsura samples and eight sequences from GenBank, including a closely-related species and common adulterants were collected. This study aimed to identify an effective DNA barcode from four popular DNA loci for P. kadsura authentication. The success rates of PCR amplification, sequencing, and sequence acquisition of matK were 10.5%, 75%, and 7.9%, respectively; for rbcL they were 89.5%, 8.8%, and 7.9%, respectively; ITS2 rates were 86.8%, 3.0%, and 2.6%, respectively, while for psbA-trnH they were all 100%, which is much higher than for the other three loci. The sequences were aligned using Muscle, genetic distances were computed using MEGA 5.2.2, and barcoding gap was performed using TAXON DNA. Phylogenetic analysis showed that psbA-trnH could clearly distinguish P. kadsura from its closely related species and the common adulterant. psbA-trnH was then used to evaluate the fake proportions of P. kadsura. Results showed that 18.4% of P. kadsura samples were fake, indicating that adulterant species exist in the Chinese markets. Two-dimensional DNA barcoding imaging of P. kadsura was conducted, which was beneficial to the management of P. kadsura. We conclude that the psbA-trnH region is a powerful tool for P. kadsura identification and supervision in the current medicine markets. Full article

(This article belongs to the Section Molecular Diversity)

▼ Show Figures

Graphical abstract

22 pages, 4438 KiB

Open AccessArticle

Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations

by Haiyan Qian^1,†

, Jiongjiong Chen^2,†, Youlu Pan¹ and Jianzhong Chen^1,*

¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China

² The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China

Molecules 2016, 21(9), 1222; https://doi.org/10.3390/molecules21091222 - 19 Sep 2016

Cited by 10 | Viewed by 7962

Abstract

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on [...] Read more.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors. Full article

(This article belongs to the Collection Molecular Docking)

▼ Show Figures

Graphical abstract

12 pages, 1003 KiB

Open AccessArticle

Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems

by Héctor Rudilla¹, Ester Fusté^1,2, Yolanda Cajal³

, Francesc Rabanal⁴

, Teresa Vinuesa¹ and Miguel Viñas^1,5,*

¹ Molecular Microbiology and Antibiotics, Department of Pathology and Experimental Therapeutics, Medical School-IDIBELL, University of Barcelona, Hospitalet, Barcelona 08907, Spain

² Department of Public Health, Mental Health and Perinatal Nursing, US of Nursing, University of Barcelona, Hospitalet, Barcelona 08907, Spain

³ Department of Physical Chemistry and Institute of Nanoscience and Nanotechnology, University of Barcelona, Barcelona 08028, Spain

⁴ Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain

⁵ Cooperativa De Ensino Superior Politécnico Universitário, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (CESPU, IINFACTS), Gandra 4585-116, Portugal

Molecules 2016, 21(9), 1223; https://doi.org/10.3390/molecules21091223 - 12 Sep 2016

Cited by 56 | Viewed by 9376

Abstract

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration [...] Read more.

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 μg/mL, whereas the MBEC of each antimicrobial separately was 500 μg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem. Full article

▼ Show Figures

Graphical abstract

14 pages, 1776 KiB

Open AccessArticle

HPLC-DAD-ESI-MS Analysis of Flavonoids from Leaves of Different Cultivars of Sweet Osmanthus

by Yiguang Wang, Jianxin Fu, Chao Zhang^* and Hongbo Zhao^*

Department of Ornamental Horticulture, School of Landscape Architecture, Zhejiang Agriculture and Forestry University, Lin’an 311300, China

Molecules 2016, 21(9), 1224; https://doi.org/10.3390/molecules21091224 - 14 Sep 2016

Cited by 9 | Viewed by 8888

Abstract

Osmanthus fragrans Lour. has traditionally been a popular ornamental plant in China. In this study, ethanol extracts of the leaves of four cultivar groups of O. fragrans were analyzed by high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) and high-performance liquid chromatography [...] Read more.

Osmanthus fragrans Lour. has traditionally been a popular ornamental plant in China. In this study, ethanol extracts of the leaves of four cultivar groups of O. fragrans were analyzed by high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) and high-performance liquid chromatography with electrospray ionization and mass spectrometry (HPLC-ESI-MS). The results suggest that variation in flavonoids among O. fragrans cultivars is quantitative, rather than qualitative. Fifteen components were detected and separated, among which, the structures of 11 flavonoids and two coumarins were identified or tentatively identified. According to principal component analysis (PCA) and hierarchical cluster analysis (HCA) based on the abundance of these components (expressed as rutin equivalents), 22 selected cultivars were classified into four clusters. The seven cultivars from Cluster III (‘Xiaoye Sugui’, ‘Boye Jingui’, ‘Wuyi Dangui’, ‘Yingye Dangui’, ‘Danzhuang’, ‘Foding Zhu’, and ‘Tianxiang Taige’), which are enriched in rutin and total flavonoids, and ‘Sijigui’ from Cluster II which contained the highest amounts of kaempferol glycosides and apigenin 7-O-glucoside, could be selected as potential pharmaceutical resources. However, the chemotaxonomy in this paper does not correlate with the distribution of the existing cultivar groups, demonstrating that the distribution of flavonoids in O. fragrans leaves does not provide an effective means of classification for O. fragrans cultivars based on flower color. Full article

▼ Show Figures

Graphical abstract

12 pages, 1371 KiB

Open AccessArticle

Spectroelectrochemical Study of Carbon Monoxide and Ethanol Oxidation on Pt/C, PtSn(3:1)/C and PtSn(1:1)/C Catalysts

by Rubén Rizo¹

, María Jesús Lázaro²

, Elena Pastor^1,* and Gonzalo García^1,*

¹ Departamento de Química, Instituto de Materiales y Nanotecnología, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez s/n, La Laguna 38071, Santa Cruz de Tenerife, Spain

² Instituto de Carboquímica (CSIC) Miguel Luesma Castan 4, Zaragoza 50018, Spain

Molecules 2016, 21(9), 1225; https://doi.org/10.3390/molecules21091225 - 12 Sep 2016

Cited by 27 | Viewed by 7796

Abstract

PtSn-based catalysts are one of the most active materials toward that contribute ethanol oxidation reaction (EOR). In order to gain a better understanding of the Sn influence on the carbon monoxide (principal catalyst poison) and ethanol oxidation reactions in acidic media, a systematic [...] Read more.

PtSn-based catalysts are one of the most active materials toward that contribute ethanol oxidation reaction (EOR). In order to gain a better understanding of the Sn influence on the carbon monoxide (principal catalyst poison) and ethanol oxidation reactions in acidic media, a systematic spectroelectrochemical study was carried out. With this end, carbon-supported PtSn_x (x = 0, 1/3 and 1) materials were synthesized and employed as anodic catalysts for both reactions. In situ Fourier transform infrared spectroscopy (FTIRS) and differential electrochemical mass spectrometry (DEMS) indicate that Sn diminishes the amount of bridge bonded CO (CO_B) and greatly improves the CO tolerance of Pt-based catalysts. Regarding the effect of Sn loading on the EOR, it enhances the catalytic activity and decreases the onset potential. FTIRS and DEMS analysis indicate that the C-C bond scission occurs at low overpotentials and at the same potential values regardless of the Sn loading, although the amount of C-C bond breaking decreases with the rise of Sn in the catalytic material. Therefore, the elevated catalytic activity toward the EOR at PtSn-based electrodes is mainly associated with the improved CO tolerance and the incomplete oxidation of ethanol to form acetic acid and acetaldehyde species, causing the formation of a higher amount of both C2 products with the rise of Sn loading. Full article

(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)

▼ Show Figures

Figure 1

14 pages, 1598 KiB

Open AccessArticle

Alkyl-Substituted δ-Lactones Derived from Dihydrojasmone and Their Stereoselective Fungi-Mediated Conversion: Production of New Antifeedant Agents

by Anna Gliszczyńska^1,*

, Damian Semba², Maryla Szczepanik³, Katarzyna Dancewicz⁴ and Beata Gabryś⁴

¹ Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, Wrocław 50-375, Poland

² Bioprocess and Biomedical Engineering Division, Wroclaw University of Technology, Norwida 4/6, Wrocław 50-373, Poland

³ Department of Invertebrate Zoology, Nicolaus Copernicus University, Lwowska 1, Toruń 87-100, Poland

⁴ Department of Botany and Ecology, University of Zielona Góra, Szafrana 1, Zielona Góra 65-516, Poland

Molecules 2016, 21(9), 1226; https://doi.org/10.3390/molecules21091226 - 13 Sep 2016

Cited by 2 | Viewed by 5271

Abstract

A chemoenzymatic method was applied to obtain optically pure alkyl-substituted δ-lactones. First, chemical Baeyer–Villiger oxidation of dihydrojasmone (1) was carried out, affording two new alkyl-substituted δ-lactones: 3,4-dihydro-5-methyl-6-pentyl-2H-pyran-2-one (2) and 5-methyl-6-pentyl-1,13-dioxabicyclo[4.1.0]heptan-2-one (3). In the next step, [...] Read more.

A chemoenzymatic method was applied to obtain optically pure alkyl-substituted δ-lactones. First, chemical Baeyer–Villiger oxidation of dihydrojasmone (1) was carried out, affording two new alkyl-substituted δ-lactones: 3,4-dihydro-5-methyl-6-pentyl-2H-pyran-2-one (2) and 5-methyl-6-pentyl-1,13-dioxabicyclo[4.1.0]heptan-2-one (3). In the next step, fungal strains were investigated as biocatalysts to enantioselective conversion of δ-lactones (2) and (3). The fungal cultures: Fusarium culmorum AM10, Fusarium equiseti AM15 and Beauveria bassiana AM278 catalyzed the stereoselective hydration of the double bond of lactone (2) (ee = 20%–99%) while Didymosphaeria igniaria KCh6670 proved to be the best biocatalyst for the reduction of carbonyl group in the epoxylactone (3) (ee = 99%). In both cases, chiral oxyderivatives were obtained in low to high yields (7%–91%). The synthetic lactones (2), (3) and its derivatives (4), (5) were tested for their antifeedant activity towards larvae and adults of lesser mealworm (Alphitobius diaperinus Panzer) and peach potato aphid (Myzus persicae [Sulzer]) and some of them were active towards studied insects. Full article

(This article belongs to the Special Issue Biosynthesis of Natural Products)

▼ Show Figures

Graphical abstract

25 pages, 11739 KiB

Open AccessArticle

Molecular-Based Fluorescent Nanoparticles Built from Dedicated Dipolar Thienothiophene Dyes as Ultra-Bright Green to NIR Nanoemitters

by Cristiano Mastrodonato, Paolo Pagano, Jonathan Daniel, Michel Vaultier and Mireille Blanchard-Desce^*

Institut des Sciences Moléculaires (UMR 5255 CNRS), Université de Bordeaux, 33400 Talence, France

Molecules 2016, 21(9), 1227; https://doi.org/10.3390/molecules21091227 - 14 Sep 2016

Cited by 23 | Viewed by 6766

Abstract

Fluorescent Organic Nanoparticles (FONs), prepared by self-aggregation of dedicated dyes in water, represent a promising green alternative to the toxic quantum dots (QDs) for bioimaging purposes. In the present paper, we describe the synthesis and photophysical properties of new dipolar push-pull derivatives built [...] Read more.

Fluorescent Organic Nanoparticles (FONs), prepared by self-aggregation of dedicated dyes in water, represent a promising green alternative to the toxic quantum dots (QDs) for bioimaging purposes. In the present paper, we describe the synthesis and photophysical properties of new dipolar push-pull derivatives built from thieno[3,2-b]thiophene as a π-conjugated bridge that connects a triphenylamine moiety bearing various bulky substituents as electron-releasing moiety to acceptor end-groups of increasing strength (i.e., aldehyde, dicyanovinyl and diethylthiobarbiturate). All dyes display fluorescence properties in chloroform, which shifts from the green to the NIR range depending on the molecular polarization (i.e., strength of the end-groups) as well as a large two-photon absorption (TPA) band response in the biological spectral window (700–1000 nm). The TPA bands show a bathochromic shift and hyperchromic effect with increasing polarization of the dyes with maximum TPA cross-section reaching 2000 GM for small size chromophore. All dyes are found to form stable and deeply colored nanoparticles (20–45 nm in diameter) upon nanoprecipitation in water. Although their fluorescence is strongly reduced upon aggregation, all nanoparticles show large one-photon (up to 10⁸ M⁻¹·cm⁻¹ in the visible region) and two-photon (up to 10⁶ GM in the NIR) brightness. Interestingly, both linear and non-linear optical properties are significantly affected by interchromophoric interactions, which are promoted by the molecular confinement and modulated by both the dipolar strength and the presence of the bulky groups. Finally, we exploited the photophysical properties of the FONs to design optimized core-shell nanoparticles built from a pair of complementary dipolar dyes that promotes an efficient core-to-shell FRET process. The resulting molecular-based core-shell nanoparticles combine large two-photon absorption and enhanced emission both located in the NIR spectral region, thanks to a major amplification (by a factor of 20) of the core fluorescence quantum yield. These novel nanoparticles, which combine huge one-and two-photon brightness, hold major promise for in vivo optical bioimaging. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

▼ Show Figures

Graphical abstract

15 pages, 2970 KiB

Open AccessArticle

Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

by Muhammad Yusran Abdul Aziz¹, Nadiah Abu^1,2, Swee Keong Yeap³, Wan Yong Ho⁴, Abdul Rahman Omar³, Nor Hadiani Ismail⁵, Syahida Ahmad⁶, Mehdi R. Pirozyan^3,7, Nadeem M. Akhtar⁸ and Noorjahan Banu Alitheen^1,*

¹ Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

² UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Jalan Ya’acob Latiff, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia

³ Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁴ School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor, Malaysia

⁵ Faculty of Applied Sciences, Universiti Teknologi Mara, Shah Alam 40450, Selangor, Malaysia

⁶ Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁷ School of Medical Sciences, University New South Wales, Wallace Wurth Building, Sydney, New South Wales 2052, Australia

⁸ Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Kuantan 26300, Pahang, Malaysia

Molecules 2016, 21(9), 1228; https://doi.org/10.3390/molecules21091228 - 14 Sep 2016

Cited by 24 | Viewed by 6702

Abstract

Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. [...] Read more.

Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

15 pages, 2026 KiB

Open AccessArticle

The Use of Mass Spectrometric Techniques to Differentiate Isobaric and Isomeric Flavonoid Conjugates from Axyris amaranthoides

by Łukasz Marczak^1,*, Paulina Znajdek-Awiżeń² and Wiesława Bylka²

¹ European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

² Department of Pharmacognosy, Poznan University of Medical Sciences, Świecickiego 4, 60-781 Poznan, Poland

Molecules 2016, 21(9), 1229; https://doi.org/10.3390/molecules21091229 - 19 Sep 2016

Cited by 19 | Viewed by 6814

Abstract

Flavonoids are a group of compounds that are commonly found in various plants, where they play important roles in many processes, including free radical scavenging and UV protection. These compounds can also act as chemical messengers, physiological regulators or protectants against pathogens in [...] Read more.

Flavonoids are a group of compounds that are commonly found in various plants, where they play important roles in many processes, including free radical scavenging and UV protection. These compounds can also act as chemical messengers, physiological regulators or protectants against pathogens in the defense reactions of plants. Flavonoid activity is regulated by the addition of various substituents, usually mono- or oligosaccharides of common sugars, such as glucose, rhamnose or galactose. In some plants, glucuronic acid is attached, and this sugar is often acylated by phenylpropanoic acids. Identification of these compounds and their derivatives is of great importance to understanding their role in plant metabolism and defense mechanisms; this research is important because flavonoids are frequently a significant constituent of the human diet. In this study, we identify the flavonoid conjugates present in Axyris amaranthoides L. extracts and demonstrate the usefulness of high-resolution mass spectrometry (HRMS) analyzers for the differentiation of isobaric compounds and the utility of fragmentation spectra for the differentiation of isomeric structures. According to our knowledge, some of the structures, especially dehydrodiferulated conjugates of tricin, whose structures are proposed here have been found for the first time in plant material. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

▼ Show Figures

Graphical abstract

59 pages, 5121 KiB

Open AccessArticle

Combinatorial Synthesis of Structurally Diverse Triazole-Bridged Flavonoid Dimers and Trimers

by Tze Han Sum¹, Tze Jing Sum¹, Warren R. J. D. Galloway¹, Súil Collins^1,2, David G. Twigg¹, Florian Hollfelder² and David R. Spring^1,*

¹ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK

² Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK

Molecules 2016, 21(9), 1230; https://doi.org/10.3390/molecules21091230 - 16 Sep 2016

Cited by 19 | Viewed by 10479

Abstract

Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a [...] Read more.

Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated. Full article

(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)

▼ Show Figures

Graphical abstract

2 pages, 143 KiB

Open AccessEditorial

Special Issue “Biomaterials and Bioprinting”

by Chee Kai Chua^*

, Wai Yee Yeong and Jia An

Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore

Molecules 2016, 21(9), 1231; https://doi.org/10.3390/molecules21091231 - 14 Sep 2016

Cited by 3 | Viewed by 5532

Abstract

The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm [...] Read more.

The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm shift. This Special Issue focuses on biomaterials and bioprinting and contains eight articles covering a number of recent topics in this emerging area. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

10 pages, 3960 KiB

Open AccessArticle

Identification and Characterization of Two New Degradation Products of Saikosaponin A under Acid Hydrolytic Conditions

by Jun Li, Qiang Xu and Hua Jiang^*

College of Chemistry and Pharmaceutical Engineering, Henan University of Science and Technology, Luoyang 471023, China

Molecules 2016, 21(9), 1232; https://doi.org/10.3390/molecules21091232 - 14 Sep 2016

Cited by 5 | Viewed by 4937

Abstract

Saikosaponin (SS) A is a compound with various pharmacological properties and is easily degraded into SS-B1 and SS-G under acid conditions. In the present work, two new degradation products of SS-A, formed under acid hydrolytic conditions, were detected and isolated using analytical and [...] Read more.

Saikosaponin (SS) A is a compound with various pharmacological properties and is easily degraded into SS-B1 and SS-G under acid conditions. In the present work, two new degradation products of SS-A, formed under acid hydrolytic conditions, were detected and isolated using analytical and semi-preparative liquid chromatography technology; furthermore, their structures were characterized as hydroxy-saikosaponin A and SS-B2 by spectral analysis, which is not only essential in stability-indicating method development and validation, but also could be used as a worst case scenario to assess the analytical method performance of SS-A. Moreover, their structural transformation pathways are also proposed. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

18 pages, 6676 KiB

Open AccessArticle

Structural Elucidation of a Novel Polysaccharide from Pseudostellaria heterophylla and Stimulating Glucose Uptake in Cells and Distributing in Rats by Oral

by Jinlong Chen^1,2,†, Wensheng Pang^2,†, Wentao Shi², Bin Yang², Yongjun Kan¹, Zhaodong He¹ and Juan Hu^1,2,*

¹ The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou 350003, China

² The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

Molecules 2016, 21(9), 1233; https://doi.org/10.3390/molecules21091233 - 14 Sep 2016

Cited by 34 | Viewed by 6632

Abstract

The semi-refined polysaccharide of Pseudostellaria heterophylla is a complex polysaccharide that exhibits significantly hypoglycemic activities. A novel homogeneous polysaccharide, named as H-1-2, was isolated from the semi-refined polysaccharide. The mean molecular weight of H-1-2 was 1.4 × 10⁴ Da and it was [...] Read more.

The semi-refined polysaccharide of Pseudostellaria heterophylla is a complex polysaccharide that exhibits significantly hypoglycemic activities. A novel homogeneous polysaccharide, named as H-1-2, was isolated from the semi-refined polysaccharide. The mean molecular weight of H-1-2 was 1.4 × 10⁴ Da and it was only composed of d-glucose monosaccharide. Structure elucidation indicated that H-1-2 contains pyranride, and has the characteristics of the α-iso-head configuration, a non-reducing end (T-), 4-, 1,6-, and 1,4,6-connection, in all four ways to connect glucose. H-1-2 was a type of glucan, where chemical combination exists in the main chain between 1→4 linked glucose, and contains a small amount of 1,6-linked glucose, which was in the branched chain. In vitro HepG2, 3T3-L1, and L6 cells were used to assess cellular glucose consumption and cellular glucose uptake by glucose oxidase, and the transport of 2-NBDG fluorescence probe results showed that H-1-2 could clearly increase glucose uptake and utilization in muscle and adipose cells, which is beneficial to screen for in the discovery of anti-diabetes lead compounds. H-1-2 was labeled with radioisotopes (^99mTc-pertechnetate). ^99mTc-labeled-H-1-2 was performed by SPECT/CT analysis images after oral administration in rats. At 4 h post ingestion, about 50% of the radioactivity was observed in the intestine. No significant radioactivity was found in the heart, liver, and kidney, conjecturing that absorption of ^99mTc-labeled H-1-2 might, via intestinal mucosa, be absorbed into systemic circulation. This problem, as to whether the polysaccharide is absorbed orally, will need further examination. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

▼ Show Figures

Figure 1

13 pages, 2707 KiB

Open AccessArticle

HSCCC Separation of the Two Iridoid Glycosides and Three Phenolic Compounds from Veronica ciliata and Their in Vitro Antioxidant and Anti-Hepatocarcinoma Activities

by Qiuxia Lu^1,2,†, Yiran Sun^1,2,†, Yueyue Shu^1,2, Shancai Tan^1,2, Li Yin^1,2, Yiran Guo^1,2 and Lin Tang^1,2,*

¹ Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, Sichuan, China

² National and Local Joint Engineering Laboratory for Energy Plant Bio-Oil Production and Application, Chengdu 610065, Sichuan, China

Molecules 2016, 21(9), 1234; https://doi.org/10.3390/molecules21091234 - 15 Sep 2016

Cited by 29 | Viewed by 6699

Abstract

Five main compounds, including two iridoid glycosides (catalposide, verproside) and three phenolic compounds (luteolin, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid), were separated and prepared from the crude extract of Veronica ciliata by high-speed countercurrent chromatography. n-Hexane/n-butanol/water (1.5:5:5, v/v [...] Read more.

Five main compounds, including two iridoid glycosides (catalposide, verproside) and three phenolic compounds (luteolin, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid), were separated and prepared from the crude extract of Veronica ciliata by high-speed countercurrent chromatography. n-Hexane/n-butanol/water (1.5:5:5, v/v/v) was used for the separation of catalposide and verproside. n-Hexane/n-butanol/water (3:2:5, v/v/v) was used for the separation of luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid. The head-to-tail elution mode was used with a flow rate of 5.0 mL/min and a rotary speed of 800 rpm. Finally, a total of 1.28 mg luteolin, 6 mg 4-hydroxy benzoic acid, 2 mg 3,4-dihydroxy benzoic acid, 2 mg verproside and 10 mg catalposide with purities of 98%, 99.1%, 99.5%, 99.8% and 99%, respectively, were obtained from 200 mg of crude extract. In addition, their structure was identified using MS, ¹H-NMR and ¹³C-NMR. To the best of our knowledge, this is the first report of the separation and purification of iridoid glycosides and phenolic compounds from V. ciliata by high-speed countercurrent chromatography (HSCCC). Among these compounds, luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid were separated from V. ciliata Fisch. for the first time. The results of the antioxidant activity show that protocatechuic acid and luteolin have strong antioxidant activity compared to 2,6-di-tert-butyl-4-methylphenol (BHT) and vitamin C (Vc). Five compounds also exhibited strong anti-hepatocarcinoma activities. Full article

▼ Show Figures

Figure 1

13 pages, 956 KiB

Open AccessArticle

Chemical Composition, Antibacterial and Phytotoxic Activities of Peganum harmala Seed Essential Oils from Five Different Localities in Northern Africa

by Ida Apostolico¹, Luigi Aliberti¹, Lucia Caputo¹

, Vincenzo De Feo^1,*

, Florinda Fratianni², Filomena Nazzaro²

, Lucèia Fàtima Souza^1,3 and Maroua Khadhr⁴

¹ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy

² Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche (ISA-CNR), via Roma 64, 83100 Avellino, Italy

³ Post-doctoral by National Counsel of Technological and Scientific Development, (CNPq/Brazil), 70000-000 Brasília, Brazil

⁴ Unité de Recherche de Biochimie des Lipides et Principes Actifs des Plantes, 2092 Faculté des Sciences de Tunis, Tunisa

Molecules 2016, 21(9), 1235; https://doi.org/10.3390/molecules21091235 - 15 Sep 2016

Cited by 39 | Viewed by 8152

Abstract

Peganum harmala L., also known as Syrian rue or Pègano, is a herbaceous plant belonging to the Zygohpyllaceae family, and is widely used in traditional medicine. The chemical composition of essential oils of P. harmala seeds from five different regions of Northern Africa [...] Read more.

Peganum harmala L., also known as Syrian rue or Pègano, is a herbaceous plant belonging to the Zygohpyllaceae family, and is widely used in traditional medicine. The chemical composition of essential oils of P. harmala seeds from five different regions of Northern Africa (Algeria, Egypt, Libya, Morocco and Tunisia) was studied by GC and GC-MS analyses. A total of 105 compounds were identified, the main components being oxygenated monoterpenes and oxygenated sesquiterpenes. Eugenol is the main component in all oils. The antimicrobial activity of the essential oils was assayed against some bacterial strains: Staphylococcus aureus (DSM 25693), Bacillus cereus (DSM 4313), Bacillus cereus (DSM4384), Escherichia coli (DMS 857) and Pseudomonas aeruginosa (ATCC 50071). All the oils showed different inhibitory activity. In the twentieth century this is an important result; we need possible new botanical drugs because the problem of resistance to antimicrobial drugs has become apparent. Moreover, the essential oils were evaluated for their possible in vitro phytotoxic activity against germination and initial radicle growth of Raphanus sativus L., Lepidium sativum L., and Ruta graveolens L. The results showed that both germination and radical elongation were sensitive to the oils. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

▼ Show Figures

Figure 1

15 pages, 2324 KiB

Open AccessArticle

Osimertinib (AZD9291), a Mutant-Selective EGFR Inhibitor, Reverses ABCB1-Mediated Drug Resistance in Cancer Cells

by Xiao-Yu Zhang¹, Yun-Kai Zhang¹, Yi-Jun Wang¹, Pranav Gupta¹, Leli Zeng^1,2, Megan Xu^1,†, Xiu-Qi Wang³

, Dong-Hua Yang¹ and Zhe-Sheng Chen^1,*

¹ Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA

² School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China

³ College of Animal Science, South China Agricultural University, Guangzhou 510642, China

Molecules 2016, 21(9), 1236; https://doi.org/10.3390/molecules21091236 - 15 Sep 2016

Cited by 44 | Viewed by 9286

Abstract

In recent years, tyrosine kinase inhibitors (TKIs) have been shown capable of inhibiting the ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR). In this study, we determine whether osimertinib, a novel selective, irreversible EGFR (epidermal growth factor receptor) TKI, could reverse ABC transporter-mediated MDR. [...] Read more.

In recent years, tyrosine kinase inhibitors (TKIs) have been shown capable of inhibiting the ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR). In this study, we determine whether osimertinib, a novel selective, irreversible EGFR (epidermal growth factor receptor) TKI, could reverse ABC transporter-mediated MDR. The results showed that, at non-toxic concentrations, osimertinib significantly sensitized both ABCB1-transfected and drug-selected cell lines to substrate anticancer drugs colchicine, paclitaxel, and vincristine. Osimertinib significantly increased the accumulation of [³H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. In contrast, no significant alteration in the expression levels and localization pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to 0.3 µM osimertinib for 72 h. In addition, ATPase assay showed osimertinib stimulated ABCB1 ATPase activity. Molecular docking and molecular dynamic simulations showed osimertinib has strong and stable interactions at the transmembrane domain of human homology ABCB1. Taken together, our findings suggest that osimertinib, a clinically-approved third-generation EGFR TKI, can reverse ABCB1-mediated MDR, which supports the combination therapy with osimertinib and ABCB1 substrates may potentially be a novel therapeutic stategy in ABCB1-positive drug resistant cancers. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

▼ Show Figures

Figure 1

14 pages, 1134 KiB

Open AccessArticle

ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae) and Their Antiprotozoal Activity

by Mauro S. Nogueira¹, Fernando B. Da Costa²

, Reto Brun^3,4, Marcel Kaiser^3,4 and Thomas J. Schmidt^1,*

¹ Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, Münster D-48149, Germany

² AsterBioChem Research Team, Laboratory of Pharmacognosy, School of Pharmaceutical Sciences of Ribeirão Preto, USP, Av. do Café s/n, Ribeirão Preto-SP 14040-903, Brazil

³ Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, Basel CH-4051, Switzerland

⁴ University of Basel, Petersplatz 1, Basel CH-4003, Switzerland

Molecules 2016, 21(9), 1237; https://doi.org/10.3390/molecules21091237 - 15 Sep 2016

Cited by 26 | Viewed by 6985

Abstract

Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian “Cerrado”, which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to [...] Read more.

Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian “Cerrado”, which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2), ent-2S,4S-2-19-epoxy-pimara-8(3),15-diene-7β-ol (3) and ent-7-oxo-pimara-8,15-diene-3β-ol (4), were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line). The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC

_{50}

= 3.5

μ

M) and L. donovani (IC

_{50}

= 2.5

μ

M) and ent-pimarane 2 against P. falciparum (IC

_{50}

= 3.8

μ

M). Both compounds returned high selectivity indices (SI >10) in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5), which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2

μ

g/mL). Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

▼ Show Figures

Graphical abstract

13 pages, 993 KiB

Open AccessArticle

Chemical and Sensory Evaluation of Silicone and Polylactic Acid-Based Remedial Treatments for Elevated Methoxypyrazine Levels in Wine

by Andreea Botezatu^1,2, Belinda S. Kemp^1,3

and Gary J. Pickering^1,2,3,4,5,*

¹ Cool Climate Oenology and Viticulture Institute, Brock University, St. Catharines, ON L2S 3A1, Canada

² Environmental Sustainability Research Centre, Brock University, St. Catharines, ON L2S 3A1, Canada

³ Department of Biological Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada

⁴ National Wine and Grape Industry Centre, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia

⁵ Sustainability Research Centre, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia

Molecules 2016, 21(9), 1238; https://doi.org/10.3390/molecules21091238 - 16 Sep 2016

Cited by 17 | Viewed by 6192

Abstract

Alkylmethoxypyrazines (MPs) are a class of compounds that can elicit undesirable aroma and flavor characteristics in wine, and resist remediation using traditional wine making approaches. MPs are grape-derived constituents as well as contaminants from Coccinellidae beetles present during wine processing; the latter eliciting [...] Read more.

Alkylmethoxypyrazines (MPs) are a class of compounds that can elicit undesirable aroma and flavor characteristics in wine, and resist remediation using traditional wine making approaches. MPs are grape-derived constituents as well as contaminants from Coccinellidae beetles present during wine processing; the latter eliciting an off-flavor referred to as ‘ladybug taint’. In this study we investigated the capacity of two plastic polymers—one silicone-based, the other polylactic acid-based—applied with varying surface areas to reduce concentrations of isopropylmethoxypyrazine (IPMP), sec-butylmethoxypyrazine (SBMP) and isobutylmethoxypyrazine (IBMP) in a Merlot wine using multi-dimensional gas chromatography coupled with mass spectrometry and headspace solid phase microextraction (SPME-MDGCMS). The impact of treatments on the sensory characteristics of the wine (descriptive analysis) and volatile aroma compounds (VOCs) (SPME-MDGCMS) was also investigated. Results showed substantial reductions for all of the target odorants: up to 38%, 44% and 39% for IPMP, SBMP and IBMP, respectively, for the silicone polymer, and up to 75%, 78% and 77% for IPMP, SBMP and IBMP, respectively, for the polylactic acid polymer. These polymers had no or minimal effect on VOCs at applications of 200 cm²/L for silicone or for all polylactic acid treatments. Sensory impacts were less clear, but generally showed minimal effect from the treatments. Taken overall, the data confirm the utility of both polylactic acid and silicone polymers in reducing elevated levels of grape-derived MPs, as well as potentially improving wine contaminated by ladybug taint. Full article

(This article belongs to the Collection Wine Chemistry)

▼ Show Figures

Figure 1

7 pages, 2057 KiB

Open AccessArticle

Chemical Constituents from Flueggea virosa and the Structural Revision of Dehydrochebulic Acid Trimethyl Ester

by Chih-Hua Chao^1,2,*, Ying-Ju Lin^3,4, Ju-Chien Cheng⁵, Hui-Chi Huang⁶

, Yung-Ju Yeh⁵, Tian-Shung Wu^7,8, Syh-Yuan Hwang⁹ and Yang-Chang Wu^1,2,10,11,*

¹ School of Pharmacy, China Medical University, Taichung 40402, Taiwan

² Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 40447, Taiwan

³ School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan

⁴ Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan

⁵ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan

⁶ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan

⁷ Department of Pharmacy, National Cheng Kung University, Tainan 70101, Taiwan

⁸ Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 90741, Taiwan

⁹ Endemic Species Research Institute, Council of Agriculture, Nantou 55244, Taiwan

¹⁰ Center for Molecular Medicine, China Medical University Hospital, Taichung 40447, Taiwan

¹¹ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

Show full affiliation list Hide full affiliation list

Molecules 2016, 21(9), 1239; https://doi.org/10.3390/molecules21091239 - 16 Sep 2016

Cited by 11 | Viewed by 6163

Abstract

In an attempt to study the chemical constituents from the twigs and leaves of Flueggea virosa, a new terpenoid, 9(10→20)-abeo-ent-podocarpane, 3β,10α-dihydroxy-12-methoxy-13- methyl-9(10→20)-abeo-ent-podocarpa-6,8,11,13-tetraene (1), as well as five known compounds were characterized. Their [...] Read more.

In an attempt to study the chemical constituents from the twigs and leaves of Flueggea virosa, a new terpenoid, 9(10→20)-abeo-ent-podocarpane, 3β,10α-dihydroxy-12-methoxy-13- methyl-9(10→20)-abeo-ent-podocarpa-6,8,11,13-tetraene (1), as well as five known compounds were characterized. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the structure of dehydrochebulic acid trimethyl ester was revised as (2S,3R)-4E-dehydrochebulic acid trimethyl ester based on a single-crystal X-ray diffraction study. The in vitro anti-hepatitis C virus (anti-HCV) activity and cytotoxicity against Huh7.5 cells for the isolated compounds were evaluated. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

12 pages, 1866 KiB

Open AccessArticle

A Prenylated Xanthone, Cudratricusxanthone A, Isolated from Cudrania tricuspidata Inhibits Lipopolysaccharide-Induced Neuroinflammation through Inhibition of NF-κB and p38 MAPK Pathways in BV2 Microglia

by Chi-Su Yoon^1,†, Dong-Cheol Kim^1,†, Tran Hong Quang², Jungwon Seo¹, Dae Gill Kang³, Ho Sub Lee³, Hyuncheol Oh¹ and Youn-Chul Kim^1,3,*

¹ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea

² Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi 100000, Vietnam

³ Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 54538, Korea

Molecules 2016, 21(9), 1240; https://doi.org/10.3390/molecules21091240 - 16 Sep 2016

Cited by 24 | Viewed by 7261

Abstract

Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal [...] Read more.

Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

▼ Show Figures

Figure 1

12 pages, 1223 KiB

Open AccessArticle

Xanthium strumarium as an Inhibitor of α-Glucosidase, Protein Tyrosine Phosphatase 1β, Protein Glycation and ABTS⁺ for Diabetic and Its Complication

by Seung Hwan Hwang, Zhiqiang Wang, Ha Na Yoon and Soon Sung Lim^*

Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

Molecules 2016, 21(9), 1241; https://doi.org/10.3390/molecules21091241 - 16 Sep 2016

Cited by 19 | Viewed by 7016

Abstract

Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS [...] Read more.

Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS⁺ radical scavenging activity using in vitro assays. Among the isolated compounds, methyl-3,5-di-caffeoyquinic acid exhibited significant inhibitory activity against α-glucosidase (18.42 μM), PTP1β (1.88 μM), AGEs (82.79 μM), and ABTS⁺ (6.03 μM). This effect was marked compared to that of the positive controls (acarbose 584.79 μM, sumarin 5.51 μM, aminoguanidine 1410.00 μM, and trolox 29.72 μM respectively). In addition, 3,5-di-O-CQA (88.14 μM) and protocatechuic acid (32.93 μM) had a considerable inhibitory effect against α-glucosidase and ABTS⁺. Based on these findings, methyl-3,5-di-caffeoyquinic acid was assumed to be potentially responsible for the anti-diabetic actions of X. strumarium. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

▼ Show Figures

Graphical abstract

11 pages, 3680 KiB

Open AccessArticle

Screening of Potential Xanthine Oxidase Inhibitors in Gnaphalium hypoleucum DC. by Immobilized Metal Affinity Chromatography and Ultrafiltration-Ultra Performance Liquid Chromatography-Mass Spectrometry

by Hong-Jian Zhang

, Yi-Juan Hu, Pan Xu, Wei-Qing Liang, Jie Zhou, Pei-Gang Liu, Lin Cheng and Jin-Bao Pu^*

Key Laboratory of Research and Development of Chinese Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, 132 Tianmushan Road, Hangzhou 310007, China

Molecules 2016, 21(9), 1242; https://doi.org/10.3390/molecules21091242 - 17 Sep 2016

Cited by 24 | Viewed by 7278

Abstract

In this study, a new method based on immobilized metal affinity chromatography (IMAC) combined with ultrafiltration-ultra performance liquid chromatography-mass spectrometry (UF-UPLC-MS) was developed for discovering ligands for xanthine oxidase (XO) in Gnaphalium hypoleucum DC., a folk medicine used in China for the treatment [...] Read more.

In this study, a new method based on immobilized metal affinity chromatography (IMAC) combined with ultrafiltration-ultra performance liquid chromatography-mass spectrometry (UF-UPLC-MS) was developed for discovering ligands for xanthine oxidase (XO) in Gnaphalium hypoleucum DC., a folk medicine used in China for the treatment of gout. By IMAC, the high flavonoid content of G. hypoleucum could be determined rapidly and efficiently. UF-UPLC-MS was used to select the bound xanthine oxidase ligands in the mixture and identify them. Finally, two flavonoids, luteolin-4′-O-glucoside and luteolin, were successfully screened and identified as the candidate XO inhibitors of G. hypoleucum. They were evaluated in vitro for XO inhibitory activity and their interaction mechanism was studied coupled with molecular simulations. The results were in favor of the hypothesis that the flavonoids of G. hypoleucum might be the active content for gout treatment by inhibiting XO. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

▼ Show Figures

Graphical abstract

27 pages, 495 KiB

Open AccessReview

Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

by Gabriela Mazzanti^* and Silvia Di Giacomo

Department of Physiology and Pharmacology, Sapienza—University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy

Molecules 2016, 21(9), 1243; https://doi.org/10.3390/molecules21091243 - 17 Sep 2016

Cited by 86 | Viewed by 16800

Abstract

A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), [...] Read more.

A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

▼ Show Figures

Figure 1

14 pages, 1754 KiB

Open AccessArticle

Chemical Composition and in Vitro Antimicrobial, Cytotoxic, and Central Nervous System Activities of the Essential Oils of Citrus medica L. cv. ‘Liscia’ and C. medica cv. ‘Rugosa’ Cultivated in Southern Italy

by Luigi Aliberti¹, Lucia Caputo¹

, Vincenzo De Feo^1,*

, Laura De Martino¹

, Filomena Nazzaro²

and Lucéia Fátima Souza^1,3

¹ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy

² Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche (ISA-CNR), Via Roma 64, 83100 Avellino, Italy

³ Post-Doctoral by National Counsel of Technological and Scientific Development (CNPq/Brazil), 70000-000 Brasília, Brazil

Molecules 2016, 21(9), 1244; https://doi.org/10.3390/molecules21091244 - 18 Sep 2016

Cited by 31 | Viewed by 8667

Abstract

Citrus medica cv. ‘liscia’ and C. medica cv. ‘rugosa’ are two taxa of citron, belonging to the biodiversity of South Italy, in particular of Amalfi Coast, in the Campania region. The chemical composition of the essential oils (EOs) from fruit peels of both [...] Read more.

Citrus medica cv. ‘liscia’ and C. medica cv. ‘rugosa’ are two taxa of citron, belonging to the biodiversity of South Italy, in particular of Amalfi Coast, in the Campania region. The chemical composition of the essential oils (EOs) from fruit peels of both C. medica cultivars was studied by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses. In all, 100 compounds were identified, 82 for C. medica cv. ‘liscia’, accounting for 91.4% of the total oil, and 88 for C. medica cv. ‘rugosa’, accounting for 92.0% of the total oil. Monoterpene hydrocarbons are the main constituents in both oils of C. medica cv. ‘liscia’ (79.1%) and C. medica cv. ‘rugosa’ (80.2%). In both oils, limonene (67.2%–62.8%) and camphene (8.5%–10.9%) are the main constituents. The antimicrobial activity of the EOs was assayed against some bacterial strains: Bacillus cereus (DSM 4313), Bacillus cereus (DSM 4384), Staphylococcus aureus (DSM 25693), Pseudomonas aeruginosa (ATCC 50071), and Escherichia coli (DSM 8579). Low concentrations of C. medica cv. ‘rugosa’ EO showed an inhibitory effect on P. aeruginosa and higher concentrations inhibited more B. cereus (4384) and E. coli than S. aureus. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line. The influence of the EO on the expression of adenylate cyclase 1 (ADCY1) was also studied. The antimicrobial activity registered confirm their traditional uses as food preserving agents and led us to hypothesize the possible use of these oils as antimicrobials. The alterations in ADCY1 expression suggested a role for limonene in effects on the central nervous system. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

▼ Show Figures

Figure 1

11 pages, 1228 KiB

Open AccessArticle

On the Effect of Microwave Energy on Lipase-Catalyzed Polycondensation Reactions

by Alessandro Pellis^1,2

, Georg M. Guebitz^1,3 and Thomas J. Farmer^2,*

¹ Institute for Environmental Biotechnology, University of Natural Resources and Life Sciences, Konrad Lorenz Strasse 20, 3430 Tulln an der Donau, Austria

² Green Chemistry Centre of Excellence, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK

³ Austrian Centre of Industrial Biotechnology GmbH, Konrad Lorenz Strasse 20, 3430 Tulln an der Donau, Austria

Molecules 2016, 21(9), 1245; https://doi.org/10.3390/molecules21091245 - 19 Sep 2016

Cited by 18 | Viewed by 6941

Abstract

Microwave energy (MWe) is, nowadays, widely used as a clean synthesis tool to improve several chemical reactions, such as drug molecule synthesis, carbohydrate conversion and biomass pyrolysis. On the other hand, its exploitation in enzymatic reactions has only been fleetingly investigated and, hence, [...] Read more.

Microwave energy (MWe) is, nowadays, widely used as a clean synthesis tool to improve several chemical reactions, such as drug molecule synthesis, carbohydrate conversion and biomass pyrolysis. On the other hand, its exploitation in enzymatic reactions has only been fleetingly investigated and, hence, further study of MWe is required to reach a precise understanding of its potential in this field. Starting from the authors’ experience in clean synthesis and biocatalyzed reactions, this study sheds light on the possibility of using MWe for enhancing enzyme-catalyzed polycondensation reactions and pre-polymer formation. Several systems and set ups were investigated involving bulk and organic media (solution phase) reactions, different enzymatic preparations and various starting bio-based monomers. Results show that MWe enables the biocatalyzed synthesis of polyesters and pre-polymers in a similar way to that reported using conventional heating with an oil bath, but in a few cases, notably bulk phase polycondensations under intense microwave irradiation, MWe leads to a rapid enzyme deactivation. Full article

(This article belongs to the Special Issue Chemicals from Biomass)

▼ Show Figures

Graphical abstract

11 pages, 3837 KiB

Open AccessArticle

Comparison of the Antioxidant Effects of Quercitrin and Isoquercitrin: Understanding the Role of the 6″-OH Group

by Xican Li^1,*

, Qian Jiang¹, Tingting Wang¹, Jingjing Liu¹ and Dongfeng Chen^2,*

¹ School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China

² School of Basic Medical Science, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China

Molecules 2016, 21(9), 1246; https://doi.org/10.3390/molecules21091246 - 19 Sep 2016

Cited by 146 | Viewed by 9421

Abstract

The role of the 6″-OH (ω-OH) group in the antioxidant activity of flavonoid glycosides has been largely overlooked. Herein, we selected quercitrin (quercetin-3-O-rhamnoside) and isoquercitrin (quercetin-3-O-glucoside) as model compounds to investigate the role of the 6″-OH group in several [...] Read more.

The role of the 6″-OH (ω-OH) group in the antioxidant activity of flavonoid glycosides has been largely overlooked. Herein, we selected quercitrin (quercetin-3-O-rhamnoside) and isoquercitrin (quercetin-3-O-glucoside) as model compounds to investigate the role of the 6″-OH group in several antioxidant pathways, including Fe²⁺-binding, hydrogen-donating (H-donating), and electron-transfer (ET). The results revealed that quercitrin and isoquercitrin both exhibited dose-dependent antioxidant activities. However, isoquercitrin showed higher levels of activity than quercitrin in the Fe²⁺-binding, ET-based ferric ion reducing antioxidant power, and multi-pathways-based superoxide anion-scavenging assays. In contrast, quercitrin exhibited greater activity than isoquercitrin in an H-donating-based 1,1-diphenyl-2-picrylhydrazyl radical-scavenging assay. Finally, in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl assay based on an oxidatively damaged mesenchymal stem cell (MSC) model, isoquercitrin performed more effectively as a cytoprotector than quercitrin. Based on these results, we concluded that (1) quercitrin and isoquercitrin can both indirectly (i.e., Fe²⁺-chelating or Fe²⁺-binding) and directly participate in the scavenging of reactive oxygen species (ROS) to protect MSCs against ROS-induced oxidative damage; (2) the 6″-OH group in isoquercitrin enhanced its ET and Fe²⁺-chelating abilities and lowered its H-donating abilities via steric hindrance or H-bonding compared with quercitrin; and (3) isoquercitrin exhibited higher ROS scavenging activity than quercitrin, allowing it to improve protect MSCs against ROS-induced oxidative damage. Full article

▼ Show Figures

Graphical abstract

4 pages, 164 KiB

Open AccessEditorial

Does a Graphical Abstract Bring More Visibility to Your Paper?

by Eva-Maria Pferschy-Wenzig¹, Ulrich Pferschy²

, Dongdong Wang³

, Andrei Mocan⁴ and Atanas G. Atanasov^3,5,*

¹ Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4/1, 8010 Graz, Austria

² Department of Statistics and Operations Research, University of Graz, Universitaetsstrasse 15, 8010 Graz, Austria

³ Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria

⁴ Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania

⁵ Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland

Molecules 2016, 21(9), 1247; https://doi.org/10.3390/molecules21091247 - 18 Sep 2016

Cited by 37 | Viewed by 32487

Abstract

A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a [...] Read more.

A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a convenient visual summary will facilitate readers with a clearer outline of papers that are of interest and will result in improved overall visibility of the respective publication. To test this assumption, we statistically compared publications with or without GA published in Molecules between March 2014 and March 2015 with regard to several output parameters reflecting visibility. Contrary to our expectations, manuscripts published without GA performed significantly better in terms of PDF downloads, abstract views, and total citations than manuscripts with GA. To the best of our knowledge, this is the first empirical study on the effectiveness of GA for attracting attention to scientific publications. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

▼ Show Figures

Graphical abstract

14 pages, 4297 KiB

Open AccessArticle

Asiatic Acid Attenuates Myocardial Ischemia/Reperfusion Injury via Akt/GSK-3β/HIF-1α Signaling in Rat H9c2 Cardiomyocytes

by Xiang Huang^1,†, Li Zuo^1,†, Yanni Lv², Chuqiao Chen¹, Yaqin Yang¹, Hongbo Xin¹, Yunman Li³ and Yisong Qian^1,*

¹ Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang 330031, China

² Department of Pharmacy, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang 330006, China

³ Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China

Molecules 2016, 21(9), 1248; https://doi.org/10.3390/molecules21091248 - 19 Sep 2016

Cited by 64 | Viewed by 10048

Abstract

Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this [...] Read more.

Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this study, we determined the effect of asiatic acid on myocardial ischemia/reperfusion injury and investigated the underlying mechanisms, using an in vitro rat H9c2 cardiomyocytes model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Results showed that pre-treatment with asiatic acid significantly augmented cell viability and prevented lactate dehydrogenase (LDH) release in a concentration-dependent manner after OGD/R exposure. Asiatic acid at 10 μM effectively inhibited apoptotic cell death, suppressed the activities of caspase-3 and caspase-9, and reversed Bax/Bcl-2 ratio in hypoxic H9c2 cells. In addition, asiatic acid improved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) accumulation, enhanced mitochondrial membrane potential and decreased intracellular calcium concentration. Using Western blot assay, we found that asiatic acid promoted the phosphorylation of Akt and subsequent inactivation of glycogen synthase kinase-3β (GSK-3β), and induced the expression of hypoxia-inducible factor 1α (HIF-1α) after OGD/R. The cardioprotective effects of asiatic acid were attenuated by the Akt or HIF-1α inhibitor. Taken together, these data suggested that asiatic acid exerted protective effects against OGD/R-induced apoptosis in cardiomyocytes, at least partly via the Akt/GSK-3β/HIF-1α pathway. Full article

(This article belongs to the Collection Bioactive Compounds)

▼ Show Figures

Figure 1

32 pages, 1057 KiB

Open AccessReview

Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

by Yingshan Qiu, Jenny K. W. Lam, Susan W. S. Leung and Wanling Liang^*

Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China

Molecules 2016, 21(9), 1249; https://doi.org/10.3390/molecules21091249 - 20 Sep 2016

Cited by 60 | Viewed by 10952

Abstract

RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated [...] Read more.

RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

▼ Show Figures

Graphical abstract

8 pages, 932 KiB

Open AccessCommunication

Two New Clerodane Diterpenes from Tinospora sagittata

by Guanhua Li^1,†, Wenbing Ding^1,2,†, Fanghao Wan^1,3 and Youzhi Li^1,2,*

¹ College of Plant Protection, Hunan Agricultural University, Changsha 410128, China

² Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha 410128, China

³ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Molecules 2016, 21(9), 1250; https://doi.org/10.3390/molecules21091250 - 19 Sep 2016

Cited by 14 | Viewed by 5744

Abstract

Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). [...] Read more.

Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). The structures of these compounds were determined on the basis of spectroscopic data interpretation, with that of the absolute configuration of compound 1 was assigned by experimental and calculated ECD spectra. The cytotoxicity and α-glucosidase inhibitory activities of isolated compounds were evaluated in vitro. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

16 pages, 1997 KiB

Open AccessArticle

Digital Gene Expression Profiling to Explore Differentially Expressed Genes Associated with Terpenoid Biosynthesis during Fruit Development in Litsea cubeba

by Ming Gao^1,2, Liyuan Lin^1,2, Yicun Chen^1,2 and Yangdong Wang^1,2,*

¹ State Key Laboratory of Forest Genetics and Tree Breeding, Chinese Academy of Forestry, No.1 Dong Xiaofu, Beijing 10086, China

² Research Institute of Subtropical Forestry, Chinese Academy of Forestry, No.73 Daqiao Road, Hangzhou 311400, Zhejiang Province, China

Molecules 2016, 21(9), 1251; https://doi.org/10.3390/molecules21091251 - 20 Sep 2016

Cited by 14 | Viewed by 5151

Abstract

Mountain pepper (Litsea cubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes [...] Read more.

Mountain pepper (Litsea cubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs) involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE) using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF) served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR) results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil. Full article

(This article belongs to the Section Molecular Diversity)

▼ Show Figures

Figure 1

17 pages, 1715 KiB

Open AccessReview

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy

by Gihyun Lee^1,2

and Sun Kwang Kim^1,*

¹ Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdaemoon-gu, Seoul 02447, Korea

² Department of Research and Development, National Development Institute of Korean Medicine, 94 Hwarang-ro, Gyeongsan-si, Gyeongsangbuk-do 38540, Korea

Molecules 2016, 21(9), 1252; https://doi.org/10.3390/molecules21091252 - 20 Sep 2016

Cited by 34 | Viewed by 8951

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient’s quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient’s quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options since there is no conventional remedy for CIPN. A range of medicinal herbs have multifarious effects, and they have shown some evidence of efficacy in various neurological and immunological diseases. While CIPN has multiple mechanisms of neurotoxicity, these phytomedicines might offer neuronal protection or regeneration with the multiple targets in CIPN. Thus far, researchers have investigated the therapeutic benefits of several herbs, herbal formulas, and phytochemicals in preventing the onset and progress of CIPN in animals and humans. Here, we summarize current knowledge regarding the role of phytochemicals, herb extracts, and herbal formulas in alleviating CIPN. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

12 pages, 3348 KiB

Open AccessArticle

The Suppressive Effects of Cinnamomi Cortex and Its Phytocompound Coumarin on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats

by Changmin Kim^1,†, Ji Hwan Lee^2,†

, Woojin Kim¹

, Dongxing Li³, Yangseok Kim¹, Kyungjin Lee^4,* and Sun Kwang Kim^1,2,*

¹ Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdamoon-gu, Seoul 02447, Korea

² Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 26 Kyunghee-daero, Dongdamoon-gu, Seoul 02447, Korea

³ Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 573 Xujiahui Rd., Dapiqiao, Huangpu Qu, Shanghai 200025, China

⁴ Department of Herbology, College of Korean Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdamoon-gu, Seoul 02447, Korea

Molecules 2016, 21(9), 1253; https://doi.org/10.3390/molecules21091253 - 20 Sep 2016

Cited by 45 | Viewed by 7198

Abstract

Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced [...] Read more.

Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced cold allodynia in rats and the mechanisms involved. A single oxaliplatin injection (6 mg/kg, i.p.) induced significant cold allodynia signs based on tail immersion tests using cold water (4 °C). Daily oral administration of water extract of C. Cortex (WECC) (100, 200, and 400 mg/kg) for five consecutive days following an oxaliplatin injection dose-dependently alleviated cold allodynia with only a slight difference in efficacies between the middle dose at 200 mg/kg and the highest dose at 400 mg/kg. WECC at 200 mg/kg significantly suppressed the activation of astrocytes and microglia and decreased the expression levels of IL-1β and TNF in the spinal cord after injection with oxaliplatin. Furthermore, oral administration of coumarin (10 mg/kg), a major phytocompound of C. Cortex, markedly reduced cold allodynia. These results indicate that C. Cortex has a potent anti-allodynic effect in oxaliplatin-injected rats through inhibiting spinal glial cells and pro-inflammatory cytokines. We also suggest that coumarin might play a role in the anti-allodynic effect of C. Cortex. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

▼ Show Figures

Figure 1

13 pages, 1950 KiB

Open AccessArticle

Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line

by Jian-Ru Guo¹, Qian-Qian Chen¹, Christopher Wai-Kei Lam¹, Cai-Yun Wang¹, Feng-Guo Xu², Bu-Ming Liu^3,*,† and Wei Zhang^1,*,†

¹ State Key Laboratory of Quality Research in Chinese Medicines, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China

² Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China

³ Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China

Molecules 2016, 21(9), 1254; https://doi.org/10.3390/molecules21091254 - 20 Sep 2016

Cited by 7 | Viewed by 5964

Abstract

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide [...] Read more.

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. Full article

(This article belongs to the Collection Herbal Medicine Research)

▼ Show Figures

Graphical abstract

7 pages, 935 KiB

Open AccessArticle

Silver Nanocomposite Biosynthesis: Antibacterial Activity against Multidrug-Resistant Strains of Pseudomonas aeruginosa and Acinetobacter baumannii

by Klebson Silva Santos^1,2,3

, Andriele Mendonça Barbosa¹, Luiz Pereira da Costa¹, Malone Santos Pinheiro¹, Maria Beatriz Prior Pinto Oliveira^2,*

and Francine Ferreira Padilha¹

¹ Institute of Technology and Research, Tiradentes University, Av. Murilo Dantas 300, 49032-971 Aracaju, SE, Brazil

² REQUIMTE/LAQV, Department of Chemistry Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

³ CAPES Foundation, Ministry of Education of Brazil, 70040-020 Brasília, DF, Brazil

Molecules 2016, 21(9), 1255; https://doi.org/10.3390/molecules21091255 - 20 Sep 2016

Cited by 25 | Viewed by 6390

Abstract

Bacterial resistance is an emerging public health issue that is disseminated worldwide. Silver nanocomposite can be an alternative strategy to avoid Gram-positive and Gram-negative bacteria growth, including multidrug-resistant strains. In the present study a silver nanocomposite was synthesized, using a new green chemistry [...] Read more.

Bacterial resistance is an emerging public health issue that is disseminated worldwide. Silver nanocomposite can be an alternative strategy to avoid Gram-positive and Gram-negative bacteria growth, including multidrug-resistant strains. In the present study a silver nanocomposite was synthesized, using a new green chemistry process, by the addition of silver nitrate (1.10⁻³ mol·L⁻¹) into a fermentative medium of Xanthomonas spp. to produce a xanthan gum polymer. Transmission electron microscopy (TEM) was used to evaluate the shape and size of the silver nanoparticles obtained. The silver ions in the nanocomposite were quantified by flame atomic absorption spectrometry (FAAS). The antibacterial activity of the nanomaterial against Escherichia coli (ATCC 22652), Enterococcus faecalis (ATCC 29282), Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923) was carried out using 500 mg of silver nanocomposite. Pseudomonas aeruginosa and Acinetobacter baumannii multidrug-resistant strains, isolated from hospitalized patients were also included in the study. The biosynthesized silver nanocomposite showed spherical nanoparticles with sizes smaller than 10 nm; 1 g of nanocomposite contained 49.24 µg of silver. Multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, and the other Gram-positive and Gram-negative bacteria tested, were sensitive to the silver nanocomposite (10–12.9 mm of inhibition zone). The biosynthesized silver nanocomposite seems to be a promising antibacterial agent for different applications, namely biomedical devices or topical wound coatings. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

14 pages, 6159 KiB

Open AccessArticle

Optimized Conditions for Passerini-Smiles Reactions and Applications to Benzoxazinone Syntheses

by Elodie Martinand-Lurin^1,2, Aurélie Dos Santos³, Emmanuelle Robineau², Pascal Retailleau¹, Philippe Dauban¹

, Laurence Grimaud^2,*

and Laurent El Kaïm^3,*

¹ Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198 Gif-sur-Yvette CEDEX, France

² 1 Ecole Normale Supérieure, PSL Research University, UPMC Univ. Paris 06, CNRS, Département de Chimie, PASTEUR, 24, rue Lhomond, 75005 Paris, France; 2 Sorbonne Universités, UPMC Univ. Paris 06, ENS, CNRS, PASTEUR, 75005 Paris, France

³ Laboratoire de Synthèse Organique, CNRS, Ecole Polytechnique, ENSTA ParisTech–UMR 7652, Université Paris-Saclay, 91128 Palaiseau, France

Molecules 2016, 21(9), 1257; https://doi.org/10.3390/molecules21091257 - 21 Sep 2016

Cited by 6 | Viewed by 7291

Abstract

Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between [...] Read more.

Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. Full article

(This article belongs to the Collection Heterocyclic Compounds)

▼ Show Figures

Graphical abstract

17 pages, 13176 KiB

Open AccessArticle

Antiangiogenic Effects of VH02, a Novel Urea Derivative: In Vitro and in Vivo Studies

by Suwadee Phowichit¹

, Miho Kobayashi², Yuriko Fujinoya², Yasufumi Sato², Kingkarn Sanphanya³, Opa Vajragupta³

, Linda Chularojmontri⁴ and Suvara K. Wattanapitayakul^1,*

¹ Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, 114 Sukhumvit 23, Bangkok 10110, Thailand

² Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri Ayudhya Road, Bangkok 10400, Thailand

⁴ Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, 95 Paholyotin Rd, Klongluang, Pathumthani 12120, Thailand

Molecules 2016, 21(9), 1258; https://doi.org/10.3390/molecules21091258 - 21 Sep 2016

Cited by 6 | Viewed by 6824

Abstract

Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore [...] Read more.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore the anti-angiogenic activity of VH02 both in vitro and in vivo. The in vitro assays include cell viability, capillary-like tube formation, MMP activity, and western blot analyses of signaling through VEGFR2 while the in vivo anti-angiogenic response were performed to evaluate the effect on vascularization in Matrigel plug applied in C57BL/6L mice. VH02 reduced angiogenesis behavior of EA.hy926 including cell viability, migration, adhesion, capillary-like tube formation, and MMP-2 activity induced by VEGF. Furthermore, VH02 regulated angiogenesis by directly inhibiting VEGFR2 on Tyr1175 signaling pathway leading to the inhibition of Akt-mediated cell survival and migration. Disruption of phosphorylation at VEGFR2-Tyr1175 by VH02 abolished FAK-Tyr397 signaling but not phosphorylation of p38 MAPK. This suggests that blockade of FAK by VH02 apparently associated with reduction of endothelial cell motility. Actin cytoskeleton rearrangement was diminished by VH02 in human endothelial cells. The anti-angiogenic effect of VH02 was confirmed in the in vivo model, revealing the reduction of vascular density in Matrigel plug after VH02 treatment. Additionally, the pericyte-like cells surrounding blood vessels in the plugs were significantly reduced as well as vascular density and p-Akt intensity. Our findings indicate that VH02 successfully inhibits VEGF-induced angiogenesis both in vitro and in vivo models. The compound could be further developed as an antiangiogenesis agent for cancer therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

▼ Show Figures

Figure 1

14 pages, 4098 KiB

Open AccessArticle

Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine

by Fang Lu, Ganggang Luo, Liansheng Qiao, Ludi Jiang, Gongyu Li and Yanling Zhang^*

Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China

Molecules 2016, 21(9), 1259; https://doi.org/10.3390/molecules21091259 - 21 Sep 2016

Cited by 16 | Viewed by 6689

Abstract

Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of [...] Read more.

Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. The binding site of the ATP-competition inhibitors and the allosteric inhibitors are partially overlapped in space position, so the same compound might interact with the two binding sites. Thus a novel screening strategy was essential for the discovery of pure CDK2 allosteric inhibitors. In this study, pharmacophore and molecular docking were used to screen potential CDK2 allosteric inhibitors and ATP-competition inhibitors from Traditional Chinese Medicine (TCM). In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Among the results, prostaglandin E1 and nordihydroguaiaretic acid (NDGA) were available and their growth inhibitory effect on human HepG2 cell lines was determined by MTT assay. The two compounds could substantially inhibit the growth of HepG2 cell lines with an estimated IC₅₀ of 41.223 μmol/L and 45.646 μmol/L. This study provides virtual screening strategy of allosteric compounds and a reliable method to discover potential pure CDK2 allosteric inhibitors from TCM. Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

▼ Show Figures

Figure 1

13 pages, 1786 KiB

Open AccessArticle

Effects of Dihydrophaseic Acid 3′-O-β-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation

by Eunkuk Park^1,2,†

, Mun-Chang Kim^1,†, Chun Whan Choi^3,†, Jeonghyun Kim^1,2,†, Hyun-Seok Jin⁴, Ryunjin Lee^1,2, Ji-Won Lee⁵, Jin-Hyok Park⁶, Dam Huh^6,* and Seon-Yong Jeong^1,2,*

¹ Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea

² Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea

³ Bio-Center, Gyeonggi Institute of Science & Technology Promotion, Suwon 16229, Korea

⁴ Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan 31499, Korea

⁵ Korea Food Research Institute, Seongnam 13539, Korea

⁶ Dongwoodang Pharmacy Co., Ltd., Yeongchen 38819, Korea

Molecules 2016, 21(9), 1260; https://doi.org/10.3390/molecules21091260 - 21 Sep 2016

Cited by 7 | Viewed by 7299

Abstract

Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the [...] Read more.

Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation–enhancing effect of LRC extract. A known sesquiterpene glucoside, (1′R,3′S,5′R,8′S,2Z,4E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis. Full article

(This article belongs to the Collection Herbal Medicine Research)

▼ Show Figures

Graphical abstract

14 pages, 1870 KiB

Open AccessArticle

The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes

by Rita Citraro¹, Michele Navarra^2,*

, Antonio Leo¹, Eugenio Donato Di Paola¹, Ermenegildo Santangelo¹, Pellegrino Lippiello³, Rossana Aiello¹, Emilio Russo¹

and Giovambattista De Sarro¹

¹ Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy

² Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina I-98168, Italy

³ Department of Pharmacy, University of Naples Federico II, Naples I-80131, Italy

Molecules 2016, 21(9), 1261; https://doi.org/10.3390/molecules21091261 - 21 Sep 2016

Cited by 45 | Viewed by 8589

Abstract

The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange [...] Read more.

The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABA_A receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

▼ Show Figures

Graphical abstract

22 pages, 1278 KiB

Open AccessReview

Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs

by Esmerina Tili^1,2,* and Jean-Jacques Michaille^2,3

¹ Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA

² Department of Cancer Biology and Genetics (CBG), Wexner Medical Center, The Ohio State University Wexner Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA

³ BioPerox-IL, UB-INSERM IFR #100, Université de Bourgogne-Franche Comté, Faculté Gabriel, 6 Bd. Gabriel, 21000 Dijon, France

Molecules 2016, 21(9), 1263; https://doi.org/10.3390/molecules21091263 - 21 Sep 2016

Cited by 33 | Viewed by 8419

Abstract

Recent years have seen the exploration of a puzzling number of compounds found in human diet that could be of interest for prevention or treatment of various pathologies. Although many of these natural products (NPs) have long been used as remedies, their molecular [...] Read more.

Recent years have seen the exploration of a puzzling number of compounds found in human diet that could be of interest for prevention or treatment of various pathologies. Although many of these natural products (NPs) have long been used as remedies, their molecular effects still remain elusive. With the advent of biotechnology revolution, NP studies turned from chemistry and biochemistry toward global analysis of gene expression. Hope is to use genetics to identify groups of patient for whom certain NPs or their derivatives may offer new preventive or therapeutic treatments. Recently, microRNAs have gained the statute of global regulators controlling cell homeostasis by regulating gene expression through genetic and epigenetic regulatory loops. Realization that certain plant polyphenols can modify microRNA expression and thus impact gene expression globally, initiated new, mainly in vitro studies, in particular to determine phytochemicals effects on inflammatory response, whose exacerbation has been linked to several disorders including cancer, auto-immune, metabolic, cardiovascular and neuro-inflammatory diseases. However, very few mechanistic insights have been provided, given the complexity of genetic regulatory networks implicated. In this review, we will concentrate on data showing the potential interest of some plant polyphenols in manipulating the expression of pro- and anti-inflammatory microRNAs in pathological conditions. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

▼ Show Figures

Figure 1

30 pages, 2279 KiB

Open AccessReview

Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects

by Francisco J. Olivas-Aguirre¹, Joaquín Rodrigo-García¹, Nina Del R. Martínez-Ruiz¹

, Arely I. Cárdenas-Robles², Sandra O. Mendoza-Díaz²

, Emilio Álvarez-Parrilla¹

, Gustavo A. González-Aguilar³

, Laura A. De la Rosa¹

, Arnulfo Ramos-Jiménez¹

and Abraham Wall-Medrano^1,*

¹ Instituto de Ciencias Biomédicas, Departamento de Ciencias Químico-Biológicas, Universidad Autónoma de Ciudad Juárez, Anillo Envolvente del PRONAF y Estocolmo s/n, Ciudad Juárez 32310, Chihuahua, Mexico

² Departamento de Investigación y Posgrado en Alimentos, Facultad de Química, Universidad Autónoma de Querétaro, Cerro de las Campanas s/n, Querétaro 76010, Querétaro, Mexico

³ Coordinación de Tecnología de Alimentos de Origen Vegetal, Centro de Investigación en Alimentación y Desarrollo, AC. Carretera a la Victoria km. 0.6, AP 1735, Hermosillo 83000, Sonora, Mexico

Molecules 2016, 21(9), 1264; https://doi.org/10.3390/molecules21091264 - 21 Sep 2016

Cited by 231 | Viewed by 29121

Abstract

Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to [...] Read more.

Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to fruits, but its content in raspberries and strawberries is low. It has a good radical scavenging capacity (RSC) against superoxide but not hydroxyl radicals, and its oxidative potential is pH-dependent (58 mV/pH unit). After intake, Cy3G can be metabolized (phases I, II) by oral epithelial cells, absorbed by the gastric epithelium (1%–10%) and it is gut-transformed (phase II & microbial metabolism), reaching the bloodstream (<1%) and urine (about 0.02%) in low amounts. In humans and Caco-2 cells, Cy3G’s major metabolites are protocatechuic acid and phloroglucinaldehyde which are also subjected to entero-hepatic recycling, although caffeic acid and peonidin-3-glucoside seem to be strictly produced in the large bowel and renal tissues. Solid evidence supports Cy3G’s bioactivity as DNA-RSC, gastro protective, anti-inflammatory, anti-thrombotic chemo-preventive and as an epigenetic factor, exerting protection against Helicobacter pylori infection, age-related diseases, type 2 diabetes, cardiovascular disease, metabolic syndrome and oral cancer. Most relevant mechanisms include RSC, epigenetic action, competitive protein-binding and enzyme inhibition. These and other novel aspects on Cy3G’s physical-chemistry, foodomics, and health effects are discussed. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

▼ Show Figures

Figure 1

Journal Menu

Journal Browser

Molecules, Volume 21, Issue 9 (September 2016) – 160 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI