Investigating the Tyrosinase Inhibitory Activity of 4-Bromobenzoic Acid Hydrazone-Schiff Bases: In Vitro, Molecular Structure and Docking Studies

Abstract

Fourteen hydrazone-Schiff base derivatives bearing 4-bromobenzoic acid have been successfully synthesized, characterized by means of ¹H-NMR and EI-MS spectrometry and finally evaluated for in vitro tyrosinase inhibitory activity. Among the series, five compounds 2 g, 2 k, 2 d, 2 c, and 2 n attributed potent tyrosinase inhibitors with IC₅₀ values ranging from (IC₅₀=6.07±0.40 μM) to (IC₅₀=13.15±0.09 μM) surpassing the standard drug kojic acid (IC₅₀=16.9±1.30 μM). Furthermore, the remaining compounds demonstrated significant to less inhibition. The density functional theory (DFT) study was performed to investigate various electronic properties such as geometry optimization, global reactivity parameter, frontier molecular orbitals (FMOs), molecular electrostatic potential map (MEPM), theoretical ¹H-NMR chemical shift, and nonlinear optical properties (NLO). Theoretical study shows good agreement with experimental study and NLO analysis suggest that the targeted compounds are good candidates with nonlinear optics. Furthermore, the docking studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of tyrosinase enzyme. The potent compounds observed in the current work may lead them promising candidates for future drug development.