Benzimidazole bearing thiourea analogues: Synthesis, β-glucuronidase inhibitory potential and their molecular docking study

Abstract

Sixteen benzimidazole-bearing thiourea analogues (1-16) were synthesized and tested for their β-glucuronidase inhibitory potential. All analogues showed varying degrees of activity having an IC50 value ranging between 1.9 ± 0.1 to 29.3 ± 0.6 µM as compared to standard drug D-saccharic acid 1,4-lactone (IC50 value = 48.1 ± 1.2 µM). Three of the compounds such as 7, 3 and 16 stand 1st, 2nd and 3rd ranked with IC50 values 1.9 ± 0.1, 3.6 ± 0.1, 5.7 ± 0.2 µM respectively and all other analogues showed many-fold better potency as compared to standard drug. It was observed that the number, nature, position and electron donating/withdrawing effect of substituent/s on both phenyls rings greatly affect inhibitory potential. Structure-activity relationships were established and through molecular docking study binding interactions were confirmed.