Insights into the role of potent thiadiazole based Schiff base derivatives in targeting type-II diabetes: A combine in-vitro and in-silico approaches

A novel series of varied substituted thiadiazole based Schiff base analogues (1–21) were designed and characterized using NMR (¹³C, ¹H) and HREI-mass spectrometry, and secerned against the enzymes responsible for hyperglycemia i-e α-amylase and α-glucosidase. Newly designed analogues demonstrated distinct inhibitory activities having IC₅₀= 1.10 ± 0.50 to 21.40 ± 0.20 µM (for alpha-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (for alpha-glucosidase) in contrast to acarbose a well-known marketed drug (IC₅₀ = 3.16 ± 0.22 & 4.8 ± 0.21 µM for α-amylase and α-glucosidase, respectively). Compound (20) with tri-fluoromethyl at para position of aromatic ring revealed as lead candidate among the members of synthesized series, having effective inhibitory activity against enzymes α-amylase and α-glucosidase. The excellent activity of compound (20) might be due to involvement of fluoro atom interacting via H-bonding with the active sites of enzymes α-amylase and α-glucosidase being targeted. Furthermore, for exploration of binding interactions of potent drugs, molecular docking was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.