Naphthoquinone-triazole hybrids as anti-diabetic agents: An exploration of in silico and in vitro α-glucosidase and α-amylase inhibition

Abstract

Introduction: Diabetes management requires effective inhibitors of carbohydrate-hydrolyzing enzymes such as a-glucosidase and a-amylase. This study explores naphthoquinone-triazole hybrils as potential anti-diabetic agents. Objective: The object of this study is to evaluate inhibitory activities of naphthoquinone-triazole derivatives (4a-m) against a-glucosidase and a-amylase. Methods: The derivatives were screened for enzyme inhibition using in viro assays to determine IC50 Yalues. Kinetic studies on the most potent compound (41) were performed. Homology modeling, molecular docking, and molecular dynamics simulations were employed to Investigate binding Interactions against a-glucosidase. Result: Compound 41 (R = 2 - C*H_{3} - 3 - N*O_{2}) exhibited the strongest inhibition, with ICso 1.94 0.39 nM against a-glucosidase and I*C_{50} = 0.99 plus/minus 0.52 * nM against a-amylase. Kinetic analysis revealed non-competitive Inhibition of a-glucosidase (K_{t} = 0.25nM) Computational studies confirmed stable binding of 41 to the enzyme, highlighting key molecular Interactions. Conclusion: Compound 41 is a highly potent a-glucosidase inhibitor with promising a-amylase activity, supporting its potential as a lead for developing novel anti-diabetic therapeutics tar-geting postprandial hyperglycemia.