Nitrophenylpiperazine derivatives as novel tyrosinase inhibitors: design, synthesis, and in silico evaluations

Abstract

A novel series of 4-nitrophenylpiperazine derivatives ( 4a– m) was designed and synthesized as potential tyrosinase inhibitors. Comprehensive characterization using ¹H-NMR, ¹³C-NMR, CNH, and IR techniques was performed for all target compounds. Subsequently, the derivatives were evaluated for their inhibitory activity against tyrosinase. Among them, compound 4l, featuring an indole moiety at the N−1 position of the piperazine ring, exhibited a significant tyrosinase inhibitory effect with an IC ₅₀ value of 72.55 μM. Enzyme kinetics analysis revealed that 4l displayed mixed inhibition of the tyrosinase enzymatic reaction. Molecular docking was carried out in the enzyme’s active site to further investigate the enzyme-inhibitor interactions. Based on the findings, compound 4l shows promise as a lead structure for the design of potent tyrosinase inhibitors. This study paves the way for the development of more effective tyrosinase inhibitors for potential applications in various fields.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13065-024-01167-6.