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Naphthoquinone-Triazole Hybrids As Anti-Diabetic Agents: An Exploration of in Silico and in Vitro Α-Glucosidase and Α-Amylase Inhibition Publisher



Irajie C ; Fakhrilou A ; Rasekh F ; Ghasemi M ; Hosseini S ; Hashempur MH ; Taslimi P ; Mahdavi M ; Iraji A
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Source: Letters in Drug Design and Discovery Published:2025


Abstract

Introduction Diabetes management requires effective inhibitors of carbohydrate-hydrolyzing enzymes such as α-glucosidase and α-amylase. This study explores naphthoquinone-triazole hybrids as potential anti-diabetic agents. Objective The object of this study is to evaluate inhibitory activities of naphthoquinone-triazole derivatives (4a–m) against α-glucosidase and α-amylase. Methods The derivatives were screened for enzyme inhibition using in vitro assays to determine IC50 values. Kinetic studies on the most potent compound (4 l) were performed. Homology modeling, molecular docking, and molecular dynamics simulations were employed to investigate binding interactions against α-glucosidase. Results Compound 4 l (R = 2-CH3-3-NO2) exhibited the strongest inhibition, with IC50 = 1.54 ± 0.39 nM against α-glucosidase and IC50 = 0.99 ± 0.52 nM against α-amylase. Kinetic analysis revealed non-competitive inhibition of α-glucosidase (K i = 0.25 nM). Computational studies confirmed stable binding of 4 l to the enzyme, highlighting key molecular interactions. Conclusion Compound 4 l is a highly potent α-glucosidase inhibitor with promising α-amylase activity, supporting its potential as a lead for developing novel anti-diabetic therapeutics targeting postprandial hyperglycemia. © 2025 International Life Sciences Publishers PTE, LTD, Company.
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