Synthesis, in vitro α-glucosidase, α-amylase inhibitory potential and molecular docking study of thiadiazole-sulfonamide hybrid analogues

Abstract

We have synthesized fourteen thiadiazole-sulfonamide hybrid analogues (1–14) , characterized throygh different technequies i.e., NMR, HR-EIMS, and screened against α-glucosidase and α-amylase enzymes. All analogues hava excellent inhibitory potential with IC50 values ranging from 5.50 ± 0.30 to 43.30 ± 0.40 µM (α-glucosidase) and 2.40 ± 0.30 to 21.10 ± 0.50 µM (α-amylase) as compared to standard drug acarbose (IC50 = 38.45 ± 0.80 µM & 11.12 ± 0.15 µM respectivelty). In case of α-glucosidase, analogues 7 (IC50 = 5.50 ± 0.30 µM) while in case of α-amylase, analogues 1 (IC50 = 2.40 ± 0.30 µM) are the most potent among the series. Structure-activity relationships was carried out, which mostly depend on the number, type, location, and electron-donating/withdrawing effects of the substituent(s) on the phenyl ring. To demonstrate the binding interaction of the most potent analogues with the enzyme's active sites, a molecular docking study was conducted. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected non-toxic. The compounds were synthesized by simple modes of synthesis like thiosemicarbazone, thiadiazole and finally thiadiazole-sulfonamide formation.