Substituted Benzimidazole Analogues as Potential a-Amylase Inhibitors and Radical Scavengers

Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1-31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for a-amylase inhibitory, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant a-amylase inhibition with IC50 values of 1.86 +/- 0.08 to 3.16 +/- 0.31 mu M as compared to standard acarbose (IC50 = 1.46 +/- 0.26 mu M). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC50 values in the range of 1.37 +/- 0.21 to 4.00 +/- 0.10 mu M for ABTS and 1.36 +/- 0.09 to 3.60 +/- 0.20 mu M for DPPH radical scavenging activities when compared to ascorbic acid with IC50 values of 0.72 +/- 0.21 and 0.73 +/- 0.05 mu M for ABTS and DPPH radical scavenging potentials, respectively. Structure-activity relationship (SAR) was established after critical analysis of varying substitution effects on a-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the a-amylase enzyme.