Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol-Containing Compounds.

Tyrosinases (TYRs) are copper-containing metalloenzymes present in a large diversity of species. In human, hTYR is responsible for pivotal steps in melanogenesis, catalysing the oxidation of l-tyrosine to l-DOPA and further to dopaquinone. While numerous TYR inhibitors have been reported, polyphenolic compounds tend to dominate the literature. However, many of these compounds, particularly monophenols and catechols, have been identified as alternative substrates rather than true inhibitors, given their structural similarity to natural substrates. Resorcinol-containing compounds have emerged as promising candidates to address this challenge, as the meta-dihydroxy moiety in resorcinol demonstrates resistance to TYR-mediated oxidation, while retaining the favourable interactions with copper ions provided by the hydroxy groups. Although their precise mechanism of action remains debated, resorcinol derivatives have yielded some of the most active compounds against isolated mushroom and human TYRs, as well as clinically used dermocosmetic agents like rucinol and thiamidol, which exhibited very promising effects in patients with facial melasma. This review outlines the development of resorcinol-containing TYR inhibitors, categorized by scaffold type, ranging from simple alkyl analogues to intricate synthetic derivatives. Mechanistic insights about the resorcinol-TYR interaction are also presented and debated.