Tyrosinase inhibitors: Molecular mechanisms, therapeutic potentials, and translational applications in dermatology and beyond

Tyrosinase, a type-3 copper-containing oxidase, is the rate-limiting enzyme in melanogenesis, catalysing the hydroxylation of L -tyrosine to L -DOPA and its subsequent oxidation to dopaquinone. Dysregulation of this pathway underlies hyperpigmentation disorders, including melasma, post-inflammatory hyperpigmentation, and solar lentigines, while its broader roles in neurodegenerative oxidative stress and in enzymatic browning of foods establish it as a multidisciplinary therapeutic and industrial target. The enzyme's binuclear copper active site and dynamic redox states enable diverse inhibitory strategies - copper chelation, redox modulation, covalent modification, and substrate analogue competition. Natural inhibitors such as flavonoids, stilbenes, and kojic acid remain widely studied, though limited by stability and bioavailability; semi-synthetic derivatives like deoxyarbutin offer improved safety, and synthetic scaffolds including resorcinols and thiosemicarbazones achieve sub-micromolar potency. Emerging nanotechnology-based delivery systems and multifunctional scaffolds further extend translational potential across dermatology, food preservation, agriculture, and neuroprotection. This review integrates mechanistic, structural, and therapeutic perspectives to guide the rational development of selective and effective tyrosinase inhibitors. • Tyrosinase is a type-3 copper oxidase that limits melanogenesis and influences skin colour and related disorders. • Selective, safe, multifunctional tyrosinase inhibitors with clinical and industrial uses are desirable. • This review highlights the mechanisms, therapeutic potential, and applications of tyrosinase inhibitors.