Thiadiazole based triazole/hydrazone derivatives: Synthesis, in vitro α-glucosidase inhibitory activity and in silico molecular docking study

Abstract

Thiadiazole-based hydrazide was treated with different substituted phenyl isothiocyanates and benzaldehyde to synthesize thiadiazole-based triazole/hydrazone derivatives (4a–h & 5a–n). The synthesized compounds were fully characterized via different spectroscopic techniques i.e., 1H NMR, 13C NMR and HR-ESI-MS and evaluated for in vitro α-glucosidase activity. All analogues showed moderate to good α-glucosidase inhibitory potentials having IC50 values ranged from 0.40 ± 0.10 to 13.40 ± 0.30 μM (thiadiazole-based triazole) and 0.10 ± 0.05 to 15.40 ± 0.30 μM (thiadiazole-based hydrazone) as compared to the standard drug acarbose (IC50 = 12.30 ± 1.10 μM). Derivatives 4f (IC50 = 0.40 ± 0.10 µM) and 5j (IC50 = 0.30 ± 0.05 µM) was found the most potent among the series which is many fold better than the standard drug on the basis of IC50 values. Structure activity relationship was carried out which mainly depend upon the nature, number, position, electron donating/withdrawing effect of the substituent/s on phenyl rings. In addition, molecular docking study was carried out for most active analogues in order to explore the binding interactions of synthesized scaffolds with active site of enzyme and results obtained supported the experimental data. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.