Molecules

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19 pages, 3061 KiB

Open AccessArticle

New Inhibitors of Respiratory Syncytial Virus (RSV) Replication Based on Monoterpene-Substituted Arylcoumarins

by Tatyana M. Khomenko, Anna A. Shtro, Anastasia V. Galochkina, Yulia V. Nikolaeva, Anzhelika V. Garshinina, Sophia S. Borisevich, Dina V. Korchagina, Konstantin P. Volcho and Nariman F. Salakhutdinov

Molecules 2023, 28(6), 2673; https://doi.org/10.3390/molecules28062673 - 15 Mar 2023

Cited by 5 | Viewed by 1874

Abstract

Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, [...] Read more.

Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, there are no vaccines and specific chemotherapeutic agents for the treatment of this disease, so the search for low-molecular weight compounds to combat RSV is a challenge. In this work, we have shown, for the first time, that monoterpene-substituted arylcoumarins are efficient RSV replication inhibitors at low micromolar concentrations. The most active compound has a selectivity index of about 200 and acts most effectively at the early stages of infection. The F protein of RSV is a potential target for these compounds, which is also confirmed by molecular docking and molecular dynamics simulation data. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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11 pages, 2111 KiB

Open AccessArticle

Synthesis, Structural Elucidation, and Anti-Inflammatory Activity of a Water-Soluble Derivative of Arctiin

by Xia Xu, Xiaofeng Huang, Yuedan Zheng, Xiaoling Wang, Jing Xie, Sha Liu and Kun Guo

Molecules 2023, 28(4), 1789; https://doi.org/10.3390/molecules28041789 - 14 Feb 2023

Cited by 1 | Viewed by 1343

Abstract

The poor oral bioavailability of arctiin caused by its low water solubility is the biggest obstacle in developing it as a drug. In this work, a new water-soluble glucuronide derivative of arctiin (arctigenin-4′-O-glucuronide) was synthesized through 2,2,6,6-tetramethylpiperidine 1-oxyl mediated oxidation reaction. [...] Read more.

The poor oral bioavailability of arctiin caused by its low water solubility is the biggest obstacle in developing it as a drug. In this work, a new water-soluble glucuronide derivative of arctiin (arctigenin-4′-O-glucuronide) was synthesized through 2,2,6,6-tetramethylpiperidine 1-oxyl mediated oxidation reaction. Subsequently, its anti-inflammatory effect was evaluated by mice acute lung injury model in vivo. The results showed that the glucuronide derivative of arctiin not only had better water solubility but also displayed improved anti-inflammatory activity in vivo, thus serving as an innovative compound in the drug development of arctiin. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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16 pages, 6077 KiB

Open AccessArticle

Unprecedented Elimination Reactions of Cyclic Aldols: A New Biosynthetic Pathway toward the Taiwaniaquinoid Skeleton

by Juan J. Guardia, Antonio Fernández, José Justicia, Houda Zentar, Ramón Alvarez-Manzaneda, Enrique Alvarez-Manzaneda and Rachid Chahboun

Molecules 2023, 28(4), 1524; https://doi.org/10.3390/molecules28041524 - 4 Feb 2023

Viewed by 1083

Abstract

The acid treatment of 6,7-seco-abietane dialdehydes gives, in high yield, the corresponding derivatives with the 4a-methyltetrahydrofluorene skeleton of taiwaniaquinoids. A mechanism involving the elimination of formic acid from the cyclic aldol intermediate is proposed here. This process can be postulated as a new [...] Read more.

The acid treatment of 6,7-seco-abietane dialdehydes gives, in high yield, the corresponding derivatives with the 4a-methyltetrahydrofluorene skeleton of taiwaniaquinoids. A mechanism involving the elimination of formic acid from the cyclic aldol intermediate is proposed here. This process can be postulated as a new biogenetic pathway from abietane diterpenes to taiwaniaquinoids. Using this novel reaction, the first enantiospecific synthesis of bioactive natural cupresol and taxodal has been obtained. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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15 pages, 1951 KiB

Open AccessArticle

Silica Immobilised Chloro- and Amido-Derivatives of Eremomycine as Chiral Stationary Phases for the Enantioseparation of Amino Acids by Reversed-Phase Liquid Chromatography

by Nikita Sarvin, Ruslan Puzankov, Georgii Vasiyarov, Pavel N. Nesterenko and Sergey M. Staroverov

Molecules 2023, 28(1), 85; https://doi.org/10.3390/molecules28010085 - 22 Dec 2022

Cited by 6 | Viewed by 2251

Abstract

Macrocyclic glycopeptide antibiotics immobilized on silica are one of the effective classes of stationary phases for chiral recognition and HPLC separation of a wide range of optically active compounds. Enantioselectivity primarily depends on the chemical structure of the chiral ligand, immobilization chemistry, and [...] Read more.

Macrocyclic glycopeptide antibiotics immobilized on silica are one of the effective classes of stationary phases for chiral recognition and HPLC separation of a wide range of optically active compounds. Enantioselectivity primarily depends on the chemical structure of the chiral ligand, immobilization chemistry, and separation conditions. In the present work, three new chiral stationary phases (CSPs) based on macrocyclic antibiotic eremomycin were prepared and investigated for enantioseparation of amino acids. Two eremomycin derivatives, including simple non-substituted amide and bulky adamantyl amide, provided important information on the role of the carboxylic group in the eremomycin structure in the chiral recognition mechanism concerning amino acid optical isomers. One more CSP having a chlorine atom in the same position elucidates the role of the first aromatic ring in the eremomycin structure as a crucial point for chiral recognition. CSP with immobilized chloreremomycin was the most successful among the phases prepared in this work. It was additionally investigated under various separation conditions, including the type and content of the organic solvent in the eluent, the effects of different additives, and the concentration and pH of the buffer. Importantly, an efficient enantioselective separation of amino acids was achieved with pure water as the eluent. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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16 pages, 1150 KiB

Open AccessArticle

Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives

by Irina Smirnova, Anastasiya Petrova, Gul’nara Giniyatullina, Anna Smirnova, Alexandrina Volobueva, Julia Pavlyukova, Vladimir Zarubaev, Tran Van Loc, Thao Tran Thi Phoung, Vu Thi Bich Hau, Nguyen Thi Thu Thuy, Myint Myint Khine and Oxana Kazakova

Molecules 2022, 27(23), 8499; https://doi.org/10.3390/molecules27238499 - 2 Dec 2022

Cited by 5 | Viewed by 1728

Abstract

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It [...] Read more.

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It was found that 28-homopiperazine 2 and 3-N-phthalyl 22 amides of oleanonic acid demonstrated high potency with selectivity index SI 27 (IC₅₀ 21 μM) and 42 (IC₅₀ 12 μM). Oleanonic acid aminoethylpiperazine amide 6 and C-azepano-erythrodiol 23 appeared to be the most effective compounds against DENV-1 (IC_50′s 67 and 107 μM) and -2 (IC_50′s 86 and 68 μM correspondingly) serotypes. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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21 pages, 5852 KiB

Open AccessArticle

A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity In Vivo

by Anastasiia Kotliarova, Alexandra V. Podturkina, Alla V. Pavlova, Daria S. Gorina, Anastasiya V. Lastovka, Oleg V. Ardashov, Artem D. Rogachev, Arseniy E. Izyurov, Alla B. Arefieva, Alexander V. Kulikov, Tatyana G. Tolstikova, Konstantin P. Volcho, Nariman F. Salakhutdinov and Yulia Sidorova

Molecules 2022, 27(23), 8286; https://doi.org/10.3390/molecules27238286 - 28 Nov 2022

Cited by 4 | Viewed by 2267

Abstract

Parkinson’s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression [...] Read more.

Parkinson’s disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies. The aim of this work was to evaluate the neuroprotective effects of the novel compound PA96 on dopamine neurons in vivo and in vitro, assess its ability to alleviate motor deficits in MPTP- and haloperidol-based PD models, as well as PK profile and BBB penetration. PA96 was synthesized from (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl) cyclohex-3-ene-1,2-diol (Prottremin) using the original three-step stereoselective procedure. We found that PA96: (1) supported the survival of cultured näive dopamine neurons; (2) supported the survival of MPP⁺-challenged dopamine neurons in vitro and in vivo; (3) had chemically appropriate properties (synthesis, solubility, etc.); (4) alleviated motor deficits in MPTP- and haloperidol-based models of PD; (5) penetrated the blood–brain barrier in vivo; and (6) was eliminated from the bloodstream relative rapidly. In conclusion, the present article demonstrates the identification of PA96 as a lead compound for the future development of this compound into a clinically used drug. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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16 pages, 5120 KiB

Open AccessArticle

Synthesis, Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids

by Marat K. Ibrayev, Oralgazy A. Nurkenov, Zhanar B. Rakhimberlinova, Altynaray T. Takibayeva, Irina V. Palamarchuk, Dastan M. Turdybekov, Assel A. Kelmyalene and Ivan V. Kulakov

Molecules 2022, 27(21), 7598; https://doi.org/10.3390/molecules27217598 - 5 Nov 2022

Cited by 5 | Viewed by 1808

Abstract

The interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles as well as cytisine and salsoline alkaloids were presented in this paper. It was shown that the reaction resulted in one one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. [...] Read more.

The interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles as well as cytisine and salsoline alkaloids were presented in this paper. It was shown that the reaction resulted in one one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction was affected by the presence of a base and an order in which reagents were added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity was carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking demonstrated that the compounds had insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increased the affinity of these substrates for target proteins selected. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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17 pages, 1972 KiB

Open AccessArticle

Design, Synthesis, and Bioactivity Study of Novel Tryptophan Derivatives Containing Azepine and Acylhydrazone Moieties

by Jingjing Zhang, Rongxin Yang, Lili Li, Jianhua Liu, Yuxiu Liu, Hongjian Song and Qingmin Wang

Molecules 2022, 27(19), 6700; https://doi.org/10.3390/molecules27196700 - 8 Oct 2022

Cited by 6 | Viewed by 1971

Abstract

Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing azepine and acylhydrazone moieties have been designed, synthesized, characterized, and evaluated for their biological activities. The bioassay results showed that the target compounds possessed moderate to good [...] Read more.

Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing azepine and acylhydrazone moieties have been designed, synthesized, characterized, and evaluated for their biological activities. The bioassay results showed that the target compounds possessed moderate to good antiviral activities against the tobacco mosaic virus (TMV), among which compounds 5c, 6a, 6h, 6t, 6v, and 6y exhibited higher inactivation, curative, and protection activities in vivo than that of ribavirin (40 ± 1, 37 ± 1, 39 ± 2% at 500 mg/L). Especially, 6y showed comparable activities to that of ningnanmycin (57 ± 2, 55 ± 3, 58 ± 1% at 500 mg/L). Meanwhile, we were pleased to find that almost all these derivatives showed good larvicidal activities against Plutella xylostella. Meanwhile, these derivatives also showed a broad spectrum of fungicidal activities. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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10 pages, 1518 KiB

Open AccessArticle

GC-MS/MS Determination of Steroid Hormones in Urine Using Solid-Phase Derivatization as an Alternative to Conventional Methods

by Azamat Temerdashev, Pavel Nesterenko, Ekaterina Dmitrieva, Kseniya Zhurkina and Yu-Qi Feng

Molecules 2022, 27(18), 5796; https://doi.org/10.3390/molecules27185796 - 7 Sep 2022

Cited by 8 | Viewed by 2884

Abstract

Solid-phase analytical derivatization (SPAD) is a promising hybrid sample preparation technique combining the clean-up and preconcentration of the sample in a single step. In this work, a novel SPAD method based on the preparation of trimethylsilyl (TMS) derivatives of steroid hormones (testosterone, estrone, [...] Read more.

Solid-phase analytical derivatization (SPAD) is a promising hybrid sample preparation technique combining the clean-up and preconcentration of the sample in a single step. In this work, a novel SPAD method based on the preparation of trimethylsilyl (TMS) derivatives of steroid hormones (testosterone, estrone, DHT, estriol, estradiol, and progesterone) in Phenomenex Strata C18-E (100 mg, 1 mL) cartridges has been developed and applied for their GC-MS/MS determination in human urine samples. The proposed procedure allows the detection and quantification of steroids with limits of 1.0–2.5 and 2.5–5 ng/mL, respectively. These characteristics are comparable with those obtained with a conventional liquid–liquid extraction, while the recovery of analytes in the proposed SPAD procedure is higher. The major advantages of SPAD are a short derivatization time, high efficiency, and the possibility to automatize the procedure. However, its cost-effectiveness in routine practice is still questionable. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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19 pages, 3721 KiB

Open AccessArticle

The Effect of a New N-hetero Cycle Derivative on Behavior and Inflammation against the Background of Ischemic Stroke

by Denis A. Borozdenko, Tatiana A. Shmigol, Aiarpi A. Ezdoglian, Darya I. Gonchar, Natalia. Y. Karpechenko, Dmitri N. Lyakhmun, Anastasia D. Shagina, Elvira A. Cherkashova, Daria D. Namestnikova, Ilya L. Gubskiy, Anastasia A. Chernysheva, Nina M. Kiseleva, Vadim V. Negrebetsky and Yuri I. Baukov

Molecules 2022, 27(17), 5488; https://doi.org/10.3390/molecules27175488 - 26 Aug 2022

Cited by 3 | Viewed by 2614

Abstract

Ischemic stroke triggers a whole cascade of pathological changes in the brain, one of which is postischemic inflammation. Since in such cases thrombolytic therapy is often not possible, methods that modulate inflammation and affect microglia become particularly interesting. We synthesized 3-(2-oxo-4-phenylpyrrolidin-1-yl)propane-1-sulfonate calcium(II) (Compound [...] Read more.

Ischemic stroke triggers a whole cascade of pathological changes in the brain, one of which is postischemic inflammation. Since in such cases thrombolytic therapy is often not possible, methods that modulate inflammation and affect microglia become particularly interesting. We synthesized 3-(2-oxo-4-phenylpyrrolidin-1-yl)propane-1-sulfonate calcium(II) (Compound 4) and studied its anti-inflammatory activity in in vitro and in vivo models of inflammation and ischemia. Macrophage cell line RAW 264.7 was treated with lipopolysaccharides (LPS) and Compound 4 at various dosages to study the cytokine profile using real-time PCR and cytometric bead array (CBA). Stroke in rats was simulated by the middle cerebral artery occlusion method (MCAO). Several tests were performed to characterize the neurological deficit and locomotor activity of the rats, and afterwards, postmortem, the number of astrocytes was counted using immunohistochemistry. Compound 4 in in vitro tests dose-dependently reduced the expression of interleukin-1β (IL1β), and inducible nitric oxide synthase (iNOS) genes in cell culture and increased the concentration of cytokines: interleukin-2, 4, 6 (IL-2, IL-4, and IL-6). In vivo Compound 4 increased the orienting-exploratory behavior, and reduced neurological and motor deficit. The number of astrocytes that promote and support inflammation was lower in the group treated with Compound 4. The stroke volume measured by magnetic resonance imaging (MRI) showed no difference. We have shown that Compound 4 demonstrates anti-inflammatory activity by increasing the synthesis of anti-inflammatory and reducing pro-inflammatory cytokines, and positively affects the neurological deficit in rats. Thus, Compound 4 has a high therapeutic potential in the management of patients after a stroke and requires further study of its neuroprotective properties. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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10 pages, 4441 KiB

Open AccessArticle

Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P₁) Receptor Agonists

by Sun Jun Park, Jushin Kim, Jaehwan Kim, Yoowon Kim, Elijah Hwejin Lee, Hyeon Jeong Kim, Siwon Kim, Byungeun Kim, Rium Kim, Ji Won Choi, Jong-Hyun Park and Ki Duk Park

Molecules 2022, 27(9), 2818; https://doi.org/10.3390/molecules27092818 - 28 Apr 2022

Cited by 1 | Viewed by 1818

Abstract

Sphingosine-1-phosphate-1 (S1P₁) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P₁ receptor internalization. We [...] Read more.

Sphingosine-1-phosphate-1 (S1P₁) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P₁ receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P₁ receptor internalization assay to evaluate functionally antagonistic S1P₁ receptor agonist activity. In order to synthesize derivatives with better efficacy than serinolamide A and B, new derivatives were synthesized by introducing the phenyl ring moiety of fingolimod. Among them, compounds 19 and 21 had superior S1P₁ agonistic effects to serinolamide. We also confirmed that compound 19 effectively inhibited lymphocyte outflow in peripheral lymphocyte count (PLC) assay. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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16 pages, 1777 KiB

Open AccessArticle

Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses

by Vladislav V. Fomenko, Nadezhda B. Rudometova, Olga I. Yarovaya, Artem D. Rogachev, Anastasia A. Fando, Anna V. Zaykovskaya, Nina I. Komarova, Dmitry N. Shcherbakov, Oleg V. Pyankov, Andrey G. Pokrovsky, Larisa I. Karpenko, Rinat A. Maksyutov and Nariman F. Salakhutdinov

Molecules 2022, 27(1), 295; https://doi.org/10.3390/molecules27010295 - 4 Jan 2022

Cited by 12 | Viewed by 3540

Abstract

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical [...] Read more.

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC₅₀2–8 μM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC₅₀ range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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13 pages, 2328 KiB

Open AccessArticle

Three New Isoprenylated Flavones from Artocarpus chama Stem and Their Bioactivities

by Sukanya Dej-adisai, Kedsaraporn Parndaeng, Chatchai Wattanapiromsakul and Jae Sung Hwang

Molecules 2022, 27(1), 3; https://doi.org/10.3390/molecules27010003 - 21 Dec 2021

Cited by 6 | Viewed by 2638

Abstract

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (3), and five known compounds, namely homoeriodictyol [...] Read more.

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC₅₀ of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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10 pages, 2436 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of δ-Viniferin Analogues and Isosteres

by Luce Micaela Mattio, Cecilia Pinna, Giorgia Catinella, Loana Musso, Kasandra Juliet Pedersen, Karen Angeliki Krogfelt, Sabrina Dallavalle and Andrea Pinto

Molecules 2021, 26(24), 7594; https://doi.org/10.3390/molecules26247594 - 15 Dec 2021

Cited by 4 | Viewed by 2501

Abstract

The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report [...] Read more.

The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5′-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL). Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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20 pages, 5656 KiB

Open AccessArticle

Monoterpene-Containing Substituted Coumarins as Inhibitors of Respiratory Syncytial Virus (RSV) Replication

by Tatyana M. Khomenko, Anna A. Shtro, Anastasia V. Galochkina, Yulia V. Nikolaeva, Galina D. Petukhova, Sophia S. Borisevich, Dina V. Korchagina, Konstantin P. Volcho and Nariman F. Salakhutdinov

Molecules 2021, 26(24), 7493; https://doi.org/10.3390/molecules26247493 - 10 Dec 2021

Cited by 8 | Viewed by 2846

Abstract

Respiratory syncytial virus (RSV) is a critical cause of infant mortality. However, there are no vaccines and adequate drugs for its treatment. We showed, for the first time, that O-linked coumarin–monoterpene conjugates are effective RSV inhibitors. The most potent compounds are active against [...] Read more.

Respiratory syncytial virus (RSV) is a critical cause of infant mortality. However, there are no vaccines and adequate drugs for its treatment. We showed, for the first time, that O-linked coumarin–monoterpene conjugates are effective RSV inhibitors. The most potent compounds are active against both RSV serotypes, A and B. According to the results of the time-of-addition experiment, the conjugates act at the early stages of virus cycle. Based on molecular modelling data, RSV F protein may be considered as a possible target. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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26 pages, 23729 KiB

Open AccessArticle

A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke

by Denis A. Borozdenko, Aiarpi A. Ezdoglian, Tatiana A. Shmigol, Darya I. Gonchar, Dmitri N. Lyakhmun, Dmitri V. Tarasenko, Yaroslav V. Golubev, Elvira A. Cherkashova, Daria D. Namestnikova, Ilya L. Gubskiy, Alexey A. Lagunin, Leonid V. Gubsky, Vladimir P. Chekhonin, Sophia S. Borisevich, Maxim A. Gureev, Anastasia D. Shagina, Nina M. Kiseleva, Vadim V. Negrebetsky and Yuri I. Baukov

Molecules 2021, 26(20), 6124; https://doi.org/10.3390/molecules26206124 - 11 Oct 2021

Cited by 10 | Viewed by 3140

Abstract

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety [...] Read more.

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood–brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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9 pages, 1484 KiB

Open AccessArticle

Rhytidhylides A and B, Two New Phthalide Derivatives from the Endophytic Fungus Rhytidhysteron sp. BZM-9

by Sha Zhang, Dekun Chen, Min Kuang, Weiwei Peng, Yan Chen, Jianbing Tan, Fenghua Kang, Kangping Xu and Zhenxing Zou

Molecules 2021, 26(20), 6092; https://doi.org/10.3390/molecules26206092 - 9 Oct 2021

Cited by 11 | Viewed by 1673

Abstract

Two new phthalide derivatives, rhytidhylides A (1) and B (2), together with ten known compounds (3–12) were isolated from cultures of Rhytidhysteron sp. BZM-9, an endophyte isolated from the leaves of Leptospermum brachyandrum. Their [...] Read more.

Two new phthalide derivatives, rhytidhylides A (1) and B (2), together with ten known compounds (3–12) were isolated from cultures of Rhytidhysteron sp. BZM-9, an endophyte isolated from the leaves of Leptospermum brachyandrum. Their structures were identified by an extensive analysis of NMR, HRESIMS, ECD, and through comparison with data reported in the literature. In addition, the cytotoxic activities against two human hepatoma cell lines (HepG2 and SMMC7721) and antibacterial activities against MRSA and E. coli were evaluated. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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17 pages, 4091 KiB

Open AccessArticle

The Molecular Structure and Self-Assembly Behavior of Reductive Amination of Oxidized Alginate Derivative for Hydrophobic Drug Delivery

by Xiuqiong Chen, Qingmei Zhu, Zhengyue Li, Huiqiong Yan and Qiang Lin

Molecules 2021, 26(19), 5821; https://doi.org/10.3390/molecules26195821 - 25 Sep 2021

Cited by 15 | Viewed by 2804

Abstract

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the [...] Read more.

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a ¹H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about −69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field. Full article

(This article belongs to the Special Issue Novel Natural and Derivative Products: Synthesis and Pharmacological Potential)

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