Abstract
(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1-27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against alpha-amylase and alpha-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14-17, 19, and 21-25 are structurally new. All com-pounds exhibited good to moderate inhibitory potential in terms of IC50 values ranging (IC50 = 13.02 +/- 0.04-46.90 +/- 0.05 mu M) and (IC50 = 13.09 +/- 0.08-46.44 +/- 0.24 mu M) in comparison to standard acarbose (IC50 = 12.94 +/- 0.27 mu M and 10.95 +/- 0.08 mu M), for alpha-amylase and alpha-glucosidase, re-spectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active alpha-amylase and alpha-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for alpha-amylase and alpha-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H- < , < - < , and < -H etc., against the corresponding targets.