Enzyme Inhibition, Kinetic, and Molecular Docking Studies of α-glucosidase

Author(s): Ebrahim S. Moghadam, Mohammad A. Faramarzi, Somayeh Imanparast, Mohsen Amini*

Journal Name: Current Enzyme Inhibition

Volume 16 , Issue 2 , 2020

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Abstract:

Background: Diabetes mellitus (DM) is an important global health problem especially in developed countries and insufficient lifestyle induces this phenomenon. Finding efficient treatment for DM is an interesting goal for researchers.

Objective: Herein we tried to design and synthesize a series of quinazoline derivatives and investigate their bioactivity as possible α-Glucosidase inhibitor agents.

Method: Compounds 1-14 were synthesized using a multicomponent reaction. 1HNMR, 13C NMR, MS, and IR spectroscopy were used for the characterization of synthesized compounds. α- Glucosidase inhibitory activity of compounds 1-14 was evaluated using p-nitrophenyl‐α‐Dglucopyranoside (pNPG) as a substrate of the α-glucosidase enzyme (EC3.2.1.20, Saccharomyces cerevisiae). The mechanism of inhibition of the α-glucosidase enzyme was investigated using kinetic studies. Molecular docking was also done using autodock software to find the possible mode of interaction of compound 8 and the enzyme active site.

Results: Most of the tested compounds showed higher activity in inhibition of the enzyme in comparison to the standard, acarbose. Compound 8 exerted the best activity with the IC50 value of 291.5 μM. A kinetic study indicated a competitive inhibition of the α-glucosidase enzyme by compound 8. Finally, docking studies showed the interactions between compound 8 and enzyme active site residues.

Conclusion: 2,4-Diarylquinazoline scaffold has good antidiabetic activity, so it is interesting to synthesize more 2,4-diarylquinazoline derivatives and evaluate their antidiabetic activities.

Keywords: Diabetes, docking, drug design, kinetic study, quinazoline, synthesis, α-Glucosidase.

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Article Details

VOLUME: 16
ISSUE: 2
Year: 2020
Published on: 30 June, 2020
Page: [155 - 161]
Pages: 7
DOI: 10.2174/1573408016999200415115009
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