Exploring the inhibitory activity and mechanism of cetylpyridine chloride: Unveiling a promising class of tyrosinase inhibitors

Abstract

Cetylpyridine chloride (CPC), a quaternary ammonium compound renowned for its antimicrobial properties, has emerged as a promising tyrosinase inhibitor. However, the precise mechanism of its inhibitory effects remains elusive. Therefore, this study endeavors to elucidate CPC's inhibitory effects and molecular mechanisms through spectroscopic analyses and computational molecular docking. Our findings unveil CPC as a reversible, competitive inhibitor of tyrosinase, achieved through hydrophobic interactions that effectively obstruct the enzymatic active site. These insights prompted the evaluation of 25 CPC analogs, assessing their monophenolase and diphenolase activities. Notably, this investigation unveiled a previously unreported class of tyrosinase inhibitors, making a substantial contribution to the existing literature. Furthermore, a preliminary structure-activity relationship analysis was conducted on a series of CPC analogs, indicating the necessity of a long alkyl chain with a minimum length of 14 carbons and a hydrophilic functional group. Our results demonstrate the potential for designing novel tyrosinase inhibitors with enhanced inhibitory capabilities, while also shedding light on surfactant-protein binding mechanisms.