Molecules

733 KiB

Open AccessArticle

Nutritional Value and Volatile Compounds of Black Cherry (Prunus serotina) Seeds

by Leticia García-Aguilar, Alejandra Rojas-Molina, César Ibarra-Alvarado, Juana I. Rojas-Molina, Pedro A. Vázquez-Landaverde, Francisco J. Luna-Vázquez and Miguel A. Zavala-Sánchez

Molecules 2015, 20(2), 3479-3495; https://doi.org/10.3390/molecules20023479 - 17 Feb 2015

Cited by 32 | Viewed by 9148

Abstract

Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study, [...] Read more.

Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study, nutritional and volatile analyses of black cherry seeds were carried out to determine their nutraceutical potential. Proximate analysis indicated that P. serotina raw and toasted seeds contain mostly fat, followed by protein, fiber, carbohydrates, and ash. The potassium content in black cherry raw and toasted seeds is high, and their protein digestibility-corrected amino acid scores suggest that they might represent a complementary source of proteins. Solid phase microextraction and gas chromatography/flame ionization detection/mass spectrometry analysis allowed identification of 59 and 99 volatile compounds in the raw and toasted seeds, respectively. The major volatile compounds identified in raw and toasted seeds were 2,3-butanediol and benzaldehyde, which contribute to the flavor and odor of the toasted seeds. Moreover, it has been previously demonstrated that benzaldehyde possesses a significant vasodilator effect, therefore, the presence of this compound along with oleic, linoleic, and α-eleostearic fatty acids indicate that black cherry seeds consumption might have beneficial effects on the cardiovascular system. Full article

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

1044 KiB

Open AccessReview

Nkrp1 Family, from Lectins to Protein Interacting Molecules

by Daniel Rozbeský, Ljubina Ivanova, Lucie Hernychová, Valéria Grobárová, Petr Novák and Jan Černý

Molecules 2015, 20(2), 3463-3478; https://doi.org/10.3390/molecules20023463 - 17 Feb 2015

Cited by 6 | Viewed by 7787

Abstract

The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca²⁺-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal [...] Read more.

The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca²⁺-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades. However, since 1996 there has been controversy and another article showed lack of interactions with saccharides in 1999. Nevertheless, several high affinity saccharide ligands were synthesized in order to utilize their potential in antitumor therapy. Subsequently, protein ligands were introduced as specific binders for Nkrp1 proteins and three dimensional models of receptor/protein ligand interaction were derived from crystallographic data. Finally, for at least some members of the NK cell C-type lectin-like proteins, the “sweet story” was impaired by two reports in recent years. It has been shown that the rat Nkrp1a and CD69 do not bind saccharide ligands such as GlcNAc, GalNAc, chitotetraose and saccharide derivatives (GlcNAc-PAMAM) do not directly and specifically influence cytotoxic activity of NK cells as it was previously described. Full article

(This article belongs to the Special Issue Lectins)

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4126 KiB

Open AccessReview

Analysis of Phenolic and Cyclic Compounds in Plants Using Derivatization Techniques in Combination with GC-MS-Based Metabolite Profiling

by Jens Rohloff

Molecules 2015, 20(2), 3431-3462; https://doi.org/10.3390/molecules20023431 - 17 Feb 2015

Cited by 67 | Viewed by 19145

Abstract

Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional [...] Read more.

Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional genomics and for screening purposes. Following solvent extraction and derivatization, hundreds of metabolites from different chemical groups can be characterized in one analytical run. Besides sugars, acids, and polyols, diverse phenolic and other cyclic metabolites can be efficiently detected by metabolite profiling. The review describes own results from plant research to exemplify the applicability of GC-MS profiling and concurrent detection and identification of phenolics and other cyclic structures. Full article

(This article belongs to the Section Molecular Diversity)

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3405 KiB

Open AccessArticle

Anti-Proliferative Effect and Induction of Apoptosis in Androgen-Independent Human Prostate Cancer Cells by 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

by Kamini Citalingam, Faridah Abas, Nordin H. Lajis, Iekhsan Othman and Rakesh Naidu

Molecules 2015, 20(2), 3406-3430; https://doi.org/10.3390/molecules20023406 - 17 Feb 2015

Cited by 22 | Viewed by 7995

Abstract

Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic [...] Read more.

Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC₅₀ values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer. Full article

(This article belongs to the Section Medicinal Chemistry)

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1837 KiB

Open AccessArticle

Investigation of Chemomarkers of Astragali Radix of Different Ages and Geographical Origin by NMR Profiling

by Lu Zheng, Mei Wang, Emmanuel Ibarra-Estrada, Changsheng Wu, Erica Georgina Wilson, Robert Verpoorte, Petrus Gerardus Leonardus Klinkhamer and Young Hae Choi

Molecules 2015, 20(2), 3389-3405; https://doi.org/10.3390/molecules20023389 - 17 Feb 2015

Cited by 21 | Viewed by 7880

Abstract

Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the [...] Read more.

Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the herb is produced or cultivated in various sites, including 10 different locations in China with very diverse environmental conditions. These differences affect their metabolic pools and consequently their medicinal properties. The comparative metabolic profiling of plants of different geographical origins or ages could contribute to detect biomarkers for their quality control and thus guarantee the efficacy of the herbal medicines produced with this drug. In this paper nuclear magnetic resonance spectroscopy (NMR)-based metabolomics was applied for to plants of different origins and age for this purpose. The results of this study show that in the set of samples evaluated, age is more discriminating than geographical location. The quantity of individual flavonoids and some primary metabolites contributed most to this age differentiation. On the other hand, based on the analysis of orthogonal partial least square (OPLS) modeling, the marker metabolites for the geographical origin were saponins and isoflavonoids. Full article

(This article belongs to the Section Natural Products Chemistry)

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3775 KiB

Open AccessArticle

A Density Functional Tight Binding Study of Acetic Acid Adsorption on Crystalline and Amorphous Surfaces of Titania

by Sergei Manzhos, Giacomo Giorgi and Koichi Yamashita

Molecules 2015, 20(2), 3371-3388; https://doi.org/10.3390/molecules20023371 - 17 Feb 2015

Cited by 42 | Viewed by 10196

Abstract

We present a comparative density functional tight binding study of an organic molecule attachment to TiO₂ via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO [...] Read more.

We present a comparative density functional tight binding study of an organic molecule attachment to TiO₂ via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO₂ (001), as well as to the surface of amorphous (a-) TiO₂ is compared with the same computational setup. On all surfaces, bidentate configurations are identified as providing the strongest adsorption energy, E_ads = −1.93, −2.49 and −1.09 eV for anatase, rutile and (B)-TiO₂, respectively. For monodentate configurations, the strongest E_ads = −1.06, −1.11 and −0.86 eV for anatase, rutile and (B)-TiO₂, respectively. Multiple monodentate and bidentate configurations are identified on a-TiO₂ with a distribution of adsorption energies and with the lowest energy configuration having stronger bonding than that of the crystalline counterparts, with E_ads up to −4.92 eV for bidentate and −1.83 eV for monodentate adsorption. Amorphous TiO₂ can therefore be used to achieve strong anchoring of organic molecules, such as dyes, that bind via a -COOH group. While the presence of the surface leads to a contraction of the band gap vs. the bulk, molecular adsorption caused no appreciable effect on the band structure around the gap in any of the systems. Full article

(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)

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2646 KiB

Open AccessArticle

Investigation of Structural Mimetics of Natural Phosphate Ion Binding Motifs

by Evgeny A. Kataev and Tatiana A. Shumilova

Molecules 2015, 20(2), 3354-3370; https://doi.org/10.3390/molecules20023354 - 16 Feb 2015

Cited by 8 | Viewed by 7219

Abstract

Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed [...] Read more.

Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed and synthesized and their anion binding properties in an acetonitrile solution have been determined. The structure of hosts mimics a part of the kinase active site that is responsible for the recognition of the phosphate residue. New hosts contain additional free amino groups with the aim to facilitate coordination of protonated anions, such as dihydrogen phosphate. According to spectrophotometric measurements, stepwise 1:1 and 1:2 binding modes have been observed for both receptors in the presence of acetate, hydrogen sulfate and dihydrogen phosphate. Compared with the acyclic receptor, the macrocyclic receptor has demonstrated a remarkably enhanced selectivity for dihydrogen phosphate over other anions. Fluorometric measurements have revealed different responses of the acyclic and macrocyclic receptors towards anions. However, in both cases, a 5–8 nm hypsochromic shift of fluorescence maximum has been observed upon interaction of acetate and dihydrogen phosphate with receptors. Full article

(This article belongs to the Special Issue Host-Guest Chemistry)

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1047 KiB

Open AccessArticle

Lactones with Methylcyclohexane Systems Obtained by Chemical and Microbiological Methods and Their Antimicrobial Activity

by Małgorzata Grabarczyk, Katarzyna Wińska, Wanda Mączka, Anna K. Żołnierczyk, Barbara Żarowska and Mirosław Anioł

Molecules 2015, 20(2), 3335-3353; https://doi.org/10.3390/molecules20023335 - 16 Feb 2015

Cited by 17 | Viewed by 5963

Abstract

Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on [...] Read more.

Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on their ability to convert these lactones into other products. Some of the tested fungal strains transformed chloro-, bromo- and iodolactone with a methyl group at C-5 into 2-hydroxy-5-methyl-9-oxabicyclo[4.3.0]nonan-8-one during hydrolytic dehalogenation. When the same lactones had the methyl group at C-3, no structural modifications of halolactones were observed. In most cases, the optical purity of the product was low or medium, with the highest rate for chlorolactone (45.4%) and iodolactone (45.2% and 47.6%). All of the obtained compounds were tested with reference to their smell. Seven halolactones and the hydroxylactone obtained via biotransformation of halolactones with 5-methylcyclohexane ring were examined for their antimicrobial activity. These compounds were capable of inhibiting growth of some bacteria, yeasts and fungi. Full article

(This article belongs to the Section Medicinal Chemistry)

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731 KiB

Open AccessReview

Prevention of Protein Glycation by Natural Compounds

by Izabela Sadowska-Bartosz and Grzegorz Bartosz

Molecules 2015, 20(2), 3309-3334; https://doi.org/10.3390/molecules20023309 - 16 Feb 2015

Cited by 134 | Viewed by 12928

Abstract

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, [...] Read more.

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, available data allow to postulate that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence, ageing. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

977 KiB

Open AccessArticle

Study of Coumarin-Resveratrol Hybrids as Potent Antioxidant Compounds

by Maria J. Matos, Francisco Mura, Saleta Vazquez-Rodriguez, Fernanda Borges, Lourdes Santana, Eugenio Uriarte and Claudio Olea-Azar

Molecules 2015, 20(2), 3290-3308; https://doi.org/10.3390/molecules20023290 - 16 Feb 2015

Cited by 42 | Viewed by 9231

Abstract

In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5–8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it [...] Read more.

In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5–8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it was concluded that these derivatives are very good antioxidants, with very interesting profiles in all the performed assays. The study of the effect of the number and position of the hydroxyl groups on the antioxidant activity was the principal aim of this study. In particular, 7-hydroxy-3-(3'-hydroxy)phenylcoumarin (8) proved to be the most active and effective antioxidant of the selected series in four of the performed assays (ORAC-FL = 11.8, capacity of scavenging hydroxyl radicals = 54%, Trolox index = 2.33 and AI₃₀ index = 0.18). However, the presence of two hydroxyl groups on this molecule did not increase greatly the activity profile. Theoretical evaluation of ADME properties of all the derivatives was also carried out. All the compounds can act as potential candidates for preventing or minimizing the free radical overproduction in oxidative-stress related diseases. These preliminary findings encourage us to perform a future structural optimization of this family of compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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754 KiB

Open AccessArticle

Three New Lanostanoids from the Mushroom Ganoderma tropicum

by Shuang-Shuang Zhang, Yu-Guang Wang, Qing-Yun Ma, Sheng-Zhuo Huang, Li-Li Hu, Hao-Fu Dai, Zhi-Fang Yu and You-Xing Zhao

Molecules 2015, 20(2), 3281-3289; https://doi.org/10.3390/molecules20023281 - 16 Feb 2015

Cited by 22 | Viewed by 6665

Abstract

Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D [...] Read more.

Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D and 2D NMR spectroscopy, as well as HR-EI-MS data. Full article

(This article belongs to the Section Natural Products Chemistry)

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911 KiB

Open AccessArticle

Design, Synthesis, and Cytotoxicity of Perbutyrylated Glycosides of 4β-Triazolopodophyllotoxin Derivatives

by Cheng-Ting Zi, Zhen-Hua Liu, Gen-Tao Li, Yan Li, Jun Zhou, Zhong-Tao Ding, Jiang-Miao Hu and Zi-Hua Jiang

Molecules 2015, 20(2), 3255-3280; https://doi.org/10.3390/molecules20023255 - 16 Feb 2015

Cited by 17 | Viewed by 6261

Abstract

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some [...] Read more.

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC₅₀ values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold. Full article

(This article belongs to the Section Medicinal Chemistry)

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1208 KiB

Open AccessCommunication

Toxicity of Amorphigenin from the Seeds of Amorpha fruticosa against the Larvae of Culex pipiens pallens (Diptera: Culicidae)

by Yaping Liang, Xiuwei Li, Zumin Gu, Peiwen Qin and Mingshan Ji

Molecules 2015, 20(2), 3238-3254; https://doi.org/10.3390/molecules20023238 - 16 Feb 2015

Cited by 17 | Viewed by 7145

Abstract

The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, [...] Read more.

The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, the ethanol one exhibited the highest larvicidal activity (LC₅₀ = 22.69 mg/L). Amorphigenin (8'-hydroxyrotenone), a rotenoid compound which exhibits a strong larvicidal activity with LC₅₀ and LC₉₀values of 4.29 and 11.27 mg/L, respectively, was isolated from the ethanol extract by column chromatograpy. Its structure was elucidated by ¹H-NMR, UV and IR spectral data. Furthermore, investigation of amorphigenin’s effects on mitochondrial complex I activity and protein synthesis in C. pipiens pallens larvae reveals that amorphigenin decreases mitochondrial complex I activities to 65.73% at 10.45 μmol/L, compared to the control, when NADH were used as the substrate. Meanwhile, amorphigenin at 10.45 μmol/L also caused a 1.98-fold decrease in protein content, compared to the control larvae treated with acetone only. Full article

(This article belongs to the Section Natural Products Chemistry)

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768 KiB

Open AccessArticle

Isolation and Characterisation of in Vitro and Cellular Free Radical Scavenging Peptides from Corn Peptide Fractions

by Liying Wang, Long Ding, Ying Wang, Yan Zhang and Jingbo Liu

Molecules 2015, 20(2), 3221-3237; https://doi.org/10.3390/molecules20023221 - 16 Feb 2015

Cited by 60 | Viewed by 8440

Abstract

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) [...] Read more.

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) were investigated. Results indicated that CPF1 (molecular weight less than 1 kDa) and CPF2 (molecular weight between 1 and 3 kDa) exhibited good hydroxyl radical, superoxide anion radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt (ABTS) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Meanwhile, the in vitro radical scavenging activity of CPF1 was slightly higher than that of CPF2. Both CPF1 and CPF2 also exhibited significant cytoprotective effects and intracellular reactive oxygen species scavenging activity in Caco-2 cells exposed to hydrogen peroxide (H₂O₂). The amino acid composition analysis revealed that the CPF were rich in hydrophobic amino acids, which comprised of more than 45% of total amino acids. An antioxidant peptide sequence of Tyr-Phe-Cys-Leu-Thr (YFCLT) was identified from CPF1 using matrix-assisted laser desorption/ionization time-of-flight/time-of-ﬂight mass spectrometry (MALDI TOF/TOF MS). The YFCLT exhibited excellent ABTS radical scavenging activity with a 50% effective concentration (EC₅₀) value of 37.63 µM, which was much lower than that of Trolox. In conclusion, corn gluten meal might be a good source to prepare antioxidant peptides. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

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1667 KiB

Open AccessArticle

Inhibitory Effect of Triterpenoids from Dillenia serrata (Dilleniaceae) on Prostaglandin E₂ Production and Quantitative HPLC Analysis of Its Koetjapic Acid and Betulinic Acid Contents

by Juriyati Jalil, Carla W. Sabandar, Norizan Ahmat, Jamia A. Jamal, Ibrahim Jantan, Nor-Ashila Aladdin, Kartiniwati Muhammad, Fhataheya Buang, Hazni Falina Mohamad and Idin Sahidin

Molecules 2015, 20(2), 3206-3220; https://doi.org/10.3390/molecules20023206 - 16 Feb 2015

Cited by 27 | Viewed by 7725

Abstract

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E₂ (PGE₂) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated [...] Read more.

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E₂ (PGE₂) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE₂ production with IC₅₀ values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC₅₀ = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids. Full article

(This article belongs to the Section Natural Products Chemistry)

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1053 KiB

Open AccessReview

Development of Bioorthogonal Reactions and Their Applications in Bioconjugation

by Mengmeng Zheng, Li Zheng, Peiyuan Zhang, Jinbo Li and Yan Zhang

Molecules 2015, 20(2), 3190-3205; https://doi.org/10.3390/molecules20023190 - 16 Feb 2015

Cited by 42 | Viewed by 13481

Abstract

Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and [...] Read more.

Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and selective ligation under bio-compatible conditions have found diverse applications in the development of new bioconjugation strategies. The development of new bioorthogonal reactions in the past decade has been summarized with comments on their potentials as bioconjugation method in the construction of various biological probes for investigating their target biomolecules. For the applications of bioorthogonal reactions in the site-selective biomolecule conjugation, examples have been presented on the bioconjugation of protein, glycan, nucleic acids and lipids. Full article

(This article belongs to the Special Issue Bioconjugations)

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Open AccessArticle

Synthesis and Antimicrobial Activity of N-Substituted-β-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties

by Kristina Mickevičienė, Rūta Baranauskaitė, Kristina Kantminienė, Maryna Stasevych, Olena Komarovska-Porokhnyavets and Volodymyr Novikov

Molecules 2015, 20(2), 3170-3189; https://doi.org/10.3390/molecules20023170 - 13 Feb 2015

Cited by 33 | Viewed by 8077

Abstract

3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity [...] Read more.

3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity against Staphylococcus aureus and Mycobacterium luteum, whereas three compounds showed significant antifungal activity against Candida tenuis and Aspergillus niger. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Spectroscopic (FT-IR, FT-Raman, ¹H- and ¹³C-NMR), Theoretical and Microbiological Study of trans o-Coumaric Acid and Alkali Metal o-Coumarates

by Małgorzata Kowczyk-Sadowy, Renata Świsłocka, Hanna Lewandowska, Jolanta Piekut and Włodzimierz Lewandowski

Molecules 2015, 20(2), 3146-3169; https://doi.org/10.3390/molecules20023146 - 13 Feb 2015

Cited by 50 | Viewed by 10800

Abstract

This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric [...] Read more.

This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric (2-hydroxy-cinnamic) acid was studied. We investigated the relationship between the molecular structure of the tested compounds and their antimicrobial activity. Complementary molecular spectroscopic techniques such as infrared (FT-IR), Raman (FT-Raman), ultraviolet-visible (UV-VIS) and nuclear magnetic resonance (¹H- and ¹³C-NMR) were applied. Structures of the molecules were optimized and their structural characteristics were calculated by the density functional theory (DFT) using the B3LYP method with 6-311++G** as a basis set. Geometric and magnetic aromaticity indices, atomic charges, dipole moments and energies were also calculated. Theoretical parameters were compared to the experimental characteristics of investigated compounds. Correlations between certain vibrational bands and some metal parameters, such as electronegativity, ionization energy, atomic and ionic radius, were found. The microbial activity of studied compounds was tested against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Proteus vulgaris and Candida albicans. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

Potential Quality Evaluation Method for Radix Astragali Based on Sweetness Indicators

by Ke Li, Fanrong Gao, Zhenyu Li, Xuemei Qin, Haifeng Sun, Jie Xing, Lizeng Zhang and Guanhua Du

Molecules 2015, 20(2), 3129-3145; https://doi.org/10.3390/molecules20023129 - 13 Feb 2015

Cited by 7 | Viewed by 6045

Abstract

Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, [...] Read more.

Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, nor a scientific investigation of the reliability of this indicator has been conducted to date. In this study, seven kinds of sweetness components were identified in RA and a quality evaluation method based on these components was established and used to characterize the quality of 48 RA samples. The sweetness evaluation method of RA was first built based on the sweetness components, and a comprehensive evaluation index commonly used in quality control of RA was also derived, which was based on the contents of four indicators (astragaloside IV, calycosin glucoside, polysaccharides and extracts). After evaluating the correlation of these indexes the results showed that the level of sweetness exhibited a strong positive correlation with the proposed comprehensive index. Our results indicate that sweetness is one of the most important quality attributes of RA and thus provide a scientific basis for the utility of the sweetness indicator in quality assessment of this Chinese herb. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

by Hyang Yeon Kim, Mee Youn Lee, Hye Min Park, Yoo Kyoung Park, Jong Cheol Shon, Kwang-Hyeon Liu and Choong Hwan Lee

Molecules 2015, 20(2), 3107-3128; https://doi.org/10.3390/molecules20023107 - 13 Feb 2015

Cited by 36 | Viewed by 10305

Abstract

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without [...] Read more.

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. Full article

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

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Open AccessArticle

Selective C–C Coupling Reaction of Dimethylphenol to Tetramethyldiphenoquinone Using Molecular Oxygen Catalyzed by Cu Complexes Immobilized in Nanospaces of Structurally-Ordered Materials

by Zen Maeno, Takato Mitsudome, Tomoo Mizugaki, Koichiro Jitsukawa and Kiyotomi Kaneda

Molecules 2015, 20(2), 3089-3106; https://doi.org/10.3390/molecules20023089 - 12 Feb 2015

Cited by 8 | Viewed by 10140

Abstract

Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O₂ as a green oxidant. The PPI dendrimer [...] Read more.

Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O₂ as a green oxidant. The PPI dendrimer encapsulated Cu ions in the internal nanovoids to form adjacent Cu species, which exhibited significantly high catalytic activity for the regioselective coupling reaction of DMP compared to previously reported enzyme and metal complex catalysts. The magadiite-immobilized Cu complex acted as a selective heterogeneous catalyst for the oxidative C–C coupling of DMP to DPQ. This heterogeneous catalyst was recoverable from the reaction mixture by simple filtration, reusable without loss of efficiency, and applicable to a continuous flow reactor system. Detailed characterization using ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), electronic spin resonance (ESR), and X-ray absorption fine structure (XAFS) spectroscopies and the reaction mechanism investigation revealed that the high catalytic performances of these Cu catalysts were ascribed to the adjacent Cu species generated within the nanospaces of the PPI dendrimer and magadiite. Full article

(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)

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Open AccessArticle

Novel Orally Active Analgesic and Anti-Inflammatory Cyclohexyl-N-Acylhydrazone Derivatives

by Tiago Fernandes Da Silva, Walfrido Bispo Júnior, Magna Suzana Alexandre-Moreira, Fanny Nascimento Costa, Carlos Eduardo da Silva Monteiro, Fabio Furlan Ferreira, Regina Cely Rodrigues Barroso, François Noël, Roberto Takashi Sudo, Gisele Zapata-Sudo, Lídia Moreira Lima and Eliezer J. Barreiro

Molecules 2015, 20(2), 3067-3088; https://doi.org/10.3390/molecules20023067 - 12 Feb 2015

Cited by 42 | Viewed by 8141

Abstract

The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of [...] Read more.

The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of new analgesic and anti-inflammatory lead-candidates, a series of cyclohexyl-N-acylhydrazones 10–26 were structurally designed from molecular modification on the prototype LASSBio-294, representing a new class of cycloalkyl analogues. Compounds 10–26 and their conformationally restricted analogue 9 were synthetized and evaluated as analgesic and anti-inflammatory agents in classical pharmacologic protocols. The cyclohexyl-N-acylhydrazones 10–26 and the cyclohexenyl analogue 9 showed great anti-inflammatory and/or analgesic activities, but compound 13 stood out as a new prototype to treat acute and chronic painful states due to its important analgesic activity in a neuropathic pain model. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

New Pregnane Glycosides from Gymnema sylvestre

by Rui Xu, Yu Yang, Yang Zhang, Fengxia Ren, Jinlong Xu, Nengjiang Yu and Yimin Zhao

Molecules 2015, 20(2), 3050-3066; https://doi.org/10.3390/molecules20023050 - 12 Feb 2015

Cited by 16 | Viewed by 6629

Abstract

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined [...] Read more.

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Inhibitors of the AAA+ Chaperone p97

by Eli Chapman, Nick Maksim, Fabian De la Cruz and James J. La Clair

Molecules 2015, 20(2), 3027-3049; https://doi.org/10.3390/molecules20023027 - 12 Feb 2015

Cited by 76 | Viewed by 11840 | Correction

Abstract

It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory [...] Read more.

It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory myeloma and later extended to lymphoma. Its use has increased the survival rate of myeloma patients by as much as three years. This success was followed with the recent accelerated approval of the natural product derived proteasome inhibitor carfilzomib (Kyprolis^®), which is used to treat patients with bortezomib-resistant multiple myeloma. The success of these two drugs has validated protein quality control as a viable target to fight select cancers, but begs the question why are proteasome inhibitors limited to lymphoma and myeloma? More recently, these limitations have encouraged the search for additional targets within the protein quality control system that might offer heightened cancer cell specificity, enhanced clinical utility, a lower rate of resistance, reduced toxicity, and mitigated side effects. One promising target is p97, an ATPase associated with various cellular activities (AAA+) chaperone. p97 figures prominently in protein quality control as well as serving a variety of other cellular functions associated with cancer. More than a decade ago, it was determined that up-regulation of p97 in many forms of cancer correlates with a poor clinical outcome. Since these initial discoveries, a mechanistic explanation for this observation has been partially illuminated, but details are lacking. Understandably, given this clinical correlation, myriad roles within the cell, and its importance in protein quality control, p97 has emerged as a potential therapeutic target. This review provides an overview of efforts towards the discovery of small molecule inhibitors of p97, offering a synopsis of efforts that parallel the excellent reviews that currently exist on p97 structure, function, and physiology. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview

Curcumin and Omega-3 Fatty Acids Enhance NK Cell-Induced Apoptosis of Pancreatic Cancer Cells but Curcumin Inhibits Interferon-γ Production: Benefits of Omega-3 with Curcumin against Cancer

by Milan Fiala

Molecules 2015, 20(2), 3020-3026; https://doi.org/10.3390/molecules20023020 - 12 Feb 2015

Cited by 49 | Viewed by 15134

Abstract

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB [...] Read more.

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB anti-apoptotic signaling but also blocking anti-oncogenic STAT-1 signaling and interferon-γ production. In our recent study (unpublished work [1]) in pancreatic cancer cell cultures, curcuminoids enhanced cancer cell apoptosis both directly and by potentiating natural killer (NK) cell cytotoxic function. The cytotoxic effects of curcuminoids were increased by incubation of cancer cells and NK cells in an emulsion with omega-3 fatty acids and antioxidants (Smartfish), which enhanced cancer cell apoptosis and protected NK cells against degradation. However, as also shown by others, curcuminoids blocked interferon-γ production by NK cells. The combined use of curcuminoids and omega-3 in cancer immunotherapy will require deeper understanding of their in vivo interactions with the immune system. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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Open AccessArticle

Structural Analysis of Metabolites of Asiatic Acid and Its Analogue Madecassic Acid in Zebrafish Using LC/IT-MSⁿ

by Binbin Xia, Lu Bai, Xiaorong Li, Jie Xiong, Pinxiang Xu and Ming Xue

Molecules 2015, 20(2), 3001-3019; https://doi.org/10.3390/molecules20023001 - 12 Feb 2015

Cited by 33 | Viewed by 10995

Abstract

Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess [...] Read more.

Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess many pharmacological effects. This study is to probe the metabolic capability of zebrafish via investigation of the drug metabolism of AA and MA in zebrafish, using a sensitive LC/IT-MSⁿ method. In addition, the main fragmentation pathways of AA and MA were reported for the first time. Nineteen metabolites of AA and MA were firstly identified after zebrafish was exposed to the drug, which all were the phase I metabolites and mainly formed from hydroxylation, dehydrogenation, hydroxylation and dehydrogenation, dihydroxylation and dehydrogenation, and dehydroxylation reaction. The results indicated that zebrafish possessed strong metabolic capacity, and the metabolites of AA and MA were formed via similar metabolic pathways and well matched with the known metabolic rules in vivo and in vitro, which supports the widely use of this system in drug metabolism research. This investigation would also contribute to the novel information on the structural elucidation, in vivo metabolites and metabolic mechanism of pentacyclic triterpenoids. Full article

(This article belongs to the Section Metabolites)

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Open AccessReview

Indole Alkaloids from Catharanthus roseus: Bioproduction and Their Effect on Human Health

by Lorena Almagro, Francisco Fernández-Pérez and Maria Angeles Pedreño

Molecules 2015, 20(2), 2973-3000; https://doi.org/10.3390/molecules20022973 - 12 Feb 2015

Cited by 196 | Viewed by 16872

Abstract

Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of [...] Read more.

Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of this plant is based on its enormous pharmaceutical interest, producing more than 130 TIAs, some of which exhibit strong pharmacological activities. The most striking biological activity investigated has been the antitumour effect of dimeric alkaloids such as anhydrovinblastine, vinblastine and vincristine which are already in pre-, clinical or in use. The great pharmacological importance of these indole alkaloids, contrasts with the small amounts of them found in this plant, making their extraction a very expensive process. To overcome this problem, researches have looked for alternative sources and strategies to produce them in higher amounts. In this sense, intensive research on the biosynthesis of TIAs and the regulation of their pathways has been developed with the aim to increase by biotechnological approaches, the production of these high added value compounds. This review is focused on the different strategies which improve TIA production, and in the analysis of the beneficial effects that these compounds exert on human health. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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Open AccessArticle

Acid Catalyzed Alcoholysis of Sulfinamides: Unusual Stereochemistry, Kinetics and a Question of Mechanism Involving Sulfurane Intermediates and Their Pseudorotation

by Bogdan Bujnicki, Józef Drabowicz and Marian Mikołajczyk

Molecules 2015, 20(2), 2949-2972; https://doi.org/10.3390/molecules20022949 - 11 Feb 2015

Cited by 11 | Viewed by 8856

Abstract

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. [...] Read more.

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations. Full article

(This article belongs to the Special Issue Dynamic Stereochemistry)

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Open AccessArticle

Inhibitory Effects of Neochamaejasmin B on P-Glycoprotein in MDCK-hMDR1 Cells and Molecular Docking of NCB Binding in P-Glycoprotein

by Lanying Pan, Haihong Hu, Xiangjun Wang, Lushan Yu, Huidi Jiang, Jianzhong Chen, Yan Lou and Su Zeng

Molecules 2015, 20(2), 2931-2948; https://doi.org/10.3390/molecules20022931 - 11 Feb 2015

Cited by 24 | Viewed by 7808

Abstract

Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed [...] Read more.

Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed to have antivirus, antitumor and antibacterial properties in China and other Asian countries. Studies were carried out to characterize the inhibition of neochamaejasmin B (NCB) on P-glycoprotein (P-gp, ABCB1, MDR1). Rhodamine-123 (R-123) transport and accumulation studies were performed in MDCK-hMDR1 cells. ABCB1 (MDR1) mRNA gene expression and P-gp protein expression were analyzed. Binding selectivity studies based on molecular docking were explored. R-123 transport and accumulation studies in MDCK-hMDR1 cells indicated that NCB inhibited the P-gp-mediated efflux in a concentration-dependent manner. RT-PCR and Western blot demonstrated that the P-gp expression was suppressed by NCB. To investigate the inhibition type of NCB on P-gp, K_i and K_i’ values were determined by double-reciprocal plots in R-123 accumulation studies. Since K_i was greater than K_i’, the inhibition of NCB on P-gp was likely a mixed type of competitive and non-competitive inhibition. The results were confirmed by molecular docking in our current work. The docking data indicated that NCB had higher affinity to P-gp than to Lig1 ((S)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one). Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Facile Access to Unnatural Dipeptide-Alcohols Based on cis-2,5-Disubstituted Pyrrolidines

by Yan-Yan Jia, Xiao-Ye Li, Ping-An Wang and Ai-Dong Wen

Molecules 2015, 20(2), 2922-2930; https://doi.org/10.3390/molecules20022922 - 11 Feb 2015

Viewed by 5910

Abstract

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, ¹H- and ¹³C-NMR spectroscopy. These unnatural dipeptide-alcohols [...] Read more.

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, ¹H- and ¹³C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Conjugated and Non Conjugated Small Molecules)

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Molecules, Volume 20, Issue 2 (February 2015) – 97 articles , Pages 1755-3495

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