Synthesis, in vitro α-glucosidase inhibitory potential and molecular docking study of thiadiazole analogs

ABSTRACTPropolis is a multi-functional bee product with a rich in polyphenols. In this study, the inhibition effect of Anatolian propolis against SARS coronavirus-2 (SARS CoV-2) was investigated asin vitroandin silico. Raw and commercial of propolis samples were used in the study and it was found that both of were rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin and caffeic acid phenethyl ester (CAPE) by HPLC-UV analysis. The ethanolic propolis extracts (EPE) were used in the screening ELISA test against the spike S1 protein (SARS Cov-2): ACE-2 inhibition KIT forin vitrostudy. Binding energy constants of these polyphenols to the CoV-2 Spike S1 RBD and ACE-2proteinwere calculated separately as molecular docking study using AutoDock 4.2 molecular docking software. In addition, pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. Binding energy constant of pinocembrin was the highest for both of the receptors, followed by chrysin, CAPE and hesperetin.In silicoADME behavior of the eight polyphenols were found potential ability to work effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against Covid-19 virus. However, further studies are needed.

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Synthesis, in vitro alpha-glucosidase inhibitory potential of benzimidazole bearing bis-Schiff bases and their molecular docking study

Bioorganic Chemistry ◽

10.1016/j.bioorg.2019.103394 ◽

2020 ◽

Vol 94 ◽

pp. 103394 ◽

Cited By ~ 6

Author(s):

Fazal Rahim ◽

Khalid Zaman ◽

Muhammad Taha ◽

Hayat Ullah ◽

Mehreen Ghufran ◽

...

Keyword(s):

Molecular Docking ◽

Schiff Bases ◽

Docking Study ◽

Molecular Docking Study ◽

Inhibitory Potential ◽

Alpha Glucosidase

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Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

Medicinal Chemistry ◽

10.2174/1573406415666190724142951 ◽

2020 ◽

Vol 16 (7) ◽

pp. 892-902 ◽

Cited By ~ 3

Author(s):

Aida Iraji ◽

Mahsima Khoshneviszadeh ◽

Pegah Bakhshizadeh ◽

Najmeh Edraki ◽

Mehdi Khoshneviszadeh

Keyword(s):

Molecular Docking ◽

Active Site ◽

Competitive Inhibition ◽

Docking Study ◽

Biological Evaluation ◽

Primary Response ◽

Ratio Method ◽

Molecular Docking Study ◽

Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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Structure analysis and biological functionalities of a nickel(II) complex and its sonochemically synthesized nano form: in vitro anti-proliferation, DNA binding, antibacterial and molecular docking study

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.129989 ◽

2021 ◽

Vol 1231 ◽

pp. 129989

Author(s):

Tahere Kondori ◽

Niloufar Akbarzadeh-T ◽

Habib Ghaznavi ◽

Zeinab Karimi ◽

Roghayeh Sheervalilou ◽

...

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Structure Analysis ◽

Docking Study ◽

Molecular Docking Study

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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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