Synthesis of New Benzimidazole-1,2,3-triazole Hybrids as Tyrosinase Inhibitors.

Abstract

A novel series of benzimidazole-1,2,3-triazole hybrids containing substituted benzyl moieties were designed, synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 2-(4-{[1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6g) and 2-(4-{[1-(4-bromobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6h) exhibited effective inhibitory activity with IC50 values of 9.42 and 10.34 μm, respectively, comparable to that of kojic acid as the reference drug (IC50 = 9.28 μm). Kinetic study of compound 6g confirmed mixed-type inhibitory activity towards tyrosinase indicating that it can bind to free enzyme as well as enzyme-substrate complex. Also, molecular docking analysis was performed to determine the binding mode of the most potent compounds (6g and 6h) in the active site of tyrosinase. Consequently, 6g and 6h derivatives might serve as promising candidates in cosmetics, medicine or food industry, and development of such compounds may be of an interest.