New benzimidazole-oxadiazole derivatives: Synthesis, α-glucosidase, α-amylase activity, and molecular modeling studies as potential antidiabetic agents

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized with different spectroscopic techniques such as H-1 NMR, C-13 NMR, and HRMS. The synthesized analogs were examined against alpha-glucosidase and alpha-amylase enzymes to determine their antidiabetic potential. Compounds 5g and 5q showed the most activity with 35.04 +/- 1.28 and 47.60 +/- 2.16 mu g/mL when compared with the reference drug acarbose (IC50 = 54.63 +/- 1.95 mu g/mL). Compounds 5g, 5o, 5s, and 5x were screened against the alpha-amylase enzyme and were found to show excellent potential, with IC50 values ranging from 22.39 +/- 1.40 to 32.07 +/- 1.55 mu g/mL, when compared with the standard acarbose (IC50 = 46.21 +/- 1.49 mu g/mL). The antioxidant activities of the effective compounds (5o, 5g, 5s, 5x, and 5q) were evaluated by TAS methods. A molecular docking research study was conducted to identify the active site and explain the functions of the active chemicals. To investigate the most likely binding mode of the substances 5g, 5o, 5q, 5s, and 5x, a molecular dynamics simulation was also carried out.

Automated summary

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized using spectroscopic techniques. The synthesized compounds were evaluated for their antidiabetic potential against alpha-glucosidase and alpha-amylase enzymes. Compounds 5g and 5q exhibited the highest activity against alpha-glucosidase, while compounds 5g, 5o, 5s, and 5x showed excellent potential against alpha-amylase. The antioxidant activities of these compounds were also evaluated, and molecular docking and dynamics simulations were performed to investigate their binding mode and mechanism.