Synthesis and Tyrosinase Inhibitory Activity of Novel Benzimidazole/Thiazolidin-4-one Hybrid Derivatives.

Abstract

In this study, novel 3-(phenylamino)thiazolidin-4-one 2 a-d and 3-(phenyl)thiazolidin-4-one 3 a-g derivatives which are having benzimidazole moiety were synthesized and their tyrosinase inhibitory activity were investigated. The structures of the target compounds were elucidated using 1 H/13 C-NMR, IR and MS. The structure of 2 b was also characterized using HSQC NMR technique. Among the target compounds, 3 b-g demonstrated stronger tyrosinase inhibitory activity (IC50 values for 3 b-g ranged from 80.93 to 119.20 μM), compared to the positive control kojic acid (IC50 : 125.08 μM). With IC50 value of 80.93 μM, 5-(2-(4-(1H-benzimidazol-1-yl)phenyl)-4-oxothiazolidin-3-yl)-2-methylbenzenesulfonamide 3 g was found to be the most active derivative of the series. Molecular docking studies were conducted to elucidate the binding interactions between compounds and tyrosinase. The MTT assay studies used to determine the cytotoxicity of 3 b-g showed that 3 c, 3 d, 3 f and 3 g were not cytotoxic in the range of 0-200 μM. Considering its tyrosinase inhibitory activity and cytotoxic effect, 3 g exhibits promising potential for further research and development as a novel tyrosinase inhibitor.