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

Abstract

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized with different spectroscopic techniques such as ¹ H NMR, ¹³ C NMR, and HRMS. The synthesized analogs were examined against α-glucosidase and α-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 µg/mL when compared with the reference drug acarbose (IC₅₀ = 54.63 ± 1.95 µg/mL). Compounds 5g, 5o, 5s, and 5x were screened against the α-amylase enzyme and were found to show excellent potential, with IC₅₀ values ranging from 22.39 ± 1.40 to 32.07 ± 1.55 µg/mL, when compared with the standard acarbose (IC₅₀ = 46.21 ± 1.49 µg/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.

Keywords: benzimidazole; molecular docking; oxadiazole; α-amylase; α-glucosidase.