Abstract

Tyrosinase mediates the production of melanin in excess, which leads to hyperpigmentation, such as melasma and melanoma to appear. Hydroquinone and kojic acid are currently limited known inhibitors, but with limitations in their stability and side effects. Therefore, safer and better alternatives and substitutes are expected. As one of the noncytotoxic substitutes, cinnamic acid and its derivatives are promising. This article compares the study results of cinnamic acid derivative inhibition activities on tyrosinase, focusing on structural modifications, mechanisms, and structure-activity relationships (SAR) to develop more effective inhibitors. Search queries were performed on the resources of Google Scholar, PubMed, and Scopus over the last 10 years (2015–2025) using similar keyword-based searches. The results of the review demonstrated that many cinnamic acid derivatives display inhibition activities that are significantly stronger than the parent compound and kojic acid. SAR analysis showed that key modification, including substitution on the phenyl ring, conversion of the carboxylate groups into esters or amides, the dimeric structure, and the essential motif of (E)-β-phenyl-α,β-unsaturated carbonyl, improve their potency. In summary, modifying cinnamic acid is a highly effective strategy to enhance the inhibitory activities of cinnamic acid derivatives towards tyrosinase, thereby producing safer and more potent inhibitors for cosmetic and therapeutic applications.

Key words: Cinnamic acid derivatives, structural modification, tyrosinase inhibitor, structure-activity relationship, hyperpigmentation