A facile approach synthesis of benzoylaryl benzimidazole as potential α-amylase and α-glucosidase inhibitor with antioxidant activity

Bioorg Chem. 2021 Sep;114:105073. doi: 10.1016/j.bioorg.2021.105073. Epub 2021 Jun 12.

Abstract

Synthetic routes to a series of benzoylarylbenzimidazol 3a-h have been derived from 3,4-diaminobenzophenone and an appropriate arylaldehyde in the presence of ammonium chloride or a mixture of ammonium chloride and sodium metabisulfite as catalyst. The antioxidant activity of targeted compounds 3a-h has been measured by four different methods and the overall antioxidant evaluation of the compounds indicated the significant MCA, FRAP, and (DPPH-SA) of the compounds except for the compound 3h. In vitro antidiabetic assay of α-amylase and α-glucosidase suggest a good to excellent activity for most tested compounds. The target benzimidazole 3f containing hydroxyl motif at para-position of phenyl revealed an important activity inhibitor against α- amylase (IC50 = 12.09 ± 0.38 µM) and α-glucosidase (IC50 = 11.02 ± 0.04 µM) comparable to the reference drug acarbose. The results of the anti hyperglycemic activity were supported by means of in silico molecular docking calculations showing strong binding affinity of compounds 3a-h with human pancreatic α-amylase (HPA) and human lysosomal acid-α-glucosidase (HLAG) active sites that confirm a good to excellent activity for most of tested compounds.

Keywords: 3,4-Diaminobenzophenone; Antioxidant activity; Aryl aldehydes; Benzoylaryl benzimidazole; α-amylase inhibitor; α-glucosidase inhibitor.