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

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 alpha-amylase and alpha-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 alpha- amylase (IC50 = 12.09 +/- 0.38 M) and alpha-glucosidase (IC50 = 11.02 +/- 0.04 mu M) 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 alpha-amylase (HPA) and human lysosomal acid-alpha-glucosidase (HLAG) active sites that confirm a good to excellent activity for most of tested compounds.

Automated summary

A series of benzoylarylbenzimidazole compounds were synthesized from specific routes and evaluated for their antioxidant and antidiabetic enzyme activities, showing significant activity for most compounds. Compound 3f exhibited remarkable inhibition against alpha-amylase and alpha-glucosidase, comparable to the reference drug acarbose. In silico molecular docking calculations confirmed the strong binding affinity of compounds 3a-h with human pancreatic alpha-amylase and human lysosomal acid-alpha-glucosidase active sites, supporting the excellent activity of most tested compounds.