Synthesis, in-vitro α-glucosidase inhibition and molecular docking studies of 1,3,4-thiadiazole-5,6-diphenyl-1,2,4-triazine hybrids: Potential leads in the search of new antidiabetic drugs

Abstract

A series of 1,3,4-thiadiazole-5,6-diphenyl-triazine hybrids 7a-l have been designed, synthesized and investigated for the α-glucosidase inhibitory activities. All the synthesized compounds 7a-l showed better inhibitory activities with IC50 values ranging between 14.36 ± 0.70 to 743.15 ± 0.86 µM in comparison with the standard drug acarbose (IC50 = 844.81 ± 0.53 µM) towards α-glucosidase. Compound 7 g with chloro substituent at the ortho position of phenyl ring at thiadiazole moiety was found to be the most active inhibitor in the series. In the kinetic analysis, the most potent compounds 7 g, 7j, 7d, 7 h and 7l exhibited mixed mode of inhibition with respect to the substrate. Furthermore, the blind molecular docking studies of all the hybrid compounds were also performed to discover the binding pose and binding interactions at the enzymatic site of α-glucosidase. The current study reveals the potential of 1,3,4-thiadiazole-5,6-diphenyl-triazine hybrids 7a-l as α-glucosidase inhibitors.