5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes

Abstract

On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC₅₀=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC₅₀=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC₅₀=12.07±0.05μM), 8 (IC₅₀=10.57±0.12μM), 11 (IC₅₀=13.76±0.02μM), 14 (IC₅₀=15.70±0.12μM) and 22 (IC₅₀=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.

Keywords: Benzimidazole; Cytotoxicity; Dual inhibitor; In silico; In vitro; Structure–activity relationship; Thiourea; Urease; α-glucosidase.