Abstract
A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by (HNMR)-H-1, C-13 NMR, MS, and screened for alpha-glucosidase inhibition. All analogs showed varied alpha-glucosidase inhibitory potential with IC50 value ranged between 0.95 +/- 0.05 to 13.60 +/- 0.30 mu M, when compared with the standard acarbose (IC50 = 1.70 +/- 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 +/- 0.05, 1.10 +/- 0.10, 1.30 +/- 0.10, 1.60 +/- 0.10, 2.30 +/- 0.10, 2.30 +/- 0.10, 2.80 +/- 0.10, 4.10 +/- 0.20 and 4.80 +/- 0.20 mu M respectively showed highest alpha-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.