Synthesis, in vitro biological assessment, and molecular docking study of benzimidazole-based thiadiazole derivatives as dual inhibitors of α-amylase and α-glucosidase

The clinical significance of benzimidazole-containing drugs has increased in the current study, making themmore effective scaffolds. Thesemoieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including H-1-NMR, C-13-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against alpha-amylase and alpha-glucosidase, all derivatives (1-17) were assessed for their biological potential. Compared to the reference drug acarbose (IC50 = 8.24 +/- 0.08 mu M), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC50 = 1.10 +/- 0.10 & 2.10 +/- 0.10 mu M, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of aamylase and alpha-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances hadwith the various amino acid residues of the targeted enzymes for this purpose.

Automated summary

The clinical significance of benzimidazole-containing drugs has increased, and research interest in these moieties is strong due to their diverse biological features. This study aimed to synthesize a new series of benzimidazole analogs and evaluate their inhibitory activity against alpha-amylase and alpha-glucosidase. Most of the derivatives showed promising activity, with analog 2 displaying the best inhibitory activity. The structure-activity relationship (SAR) was determined by examining the substitution effects, and molecular docking provided insights into the interactions between the active substances and the targeted enzymes.