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

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. The object of this study is to evaluate inhibitory activities of naphthoquinone-triazole derivatives ( 4a–m ) against α-glucosidase and α-amylase. The derivatives were screened for enzyme inhibition using in vitro assays to determine IC 50 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. Compound 4 l (R = 2-CH 3 -3-NO 2 ) exhibited the strongest inhibition, with IC 50 = 1.54 ± 0.39 nM against α-glucosidase and IC 50 = 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. 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.