Tyrosinase: a comprehensive review of its mechanism

A novel series of thirty coumarin derivatives (4a ∼ r, 5a ∼ l) constituted by coumarin and cinnamic acid/benzoic acid through oxime linkage were synthesized and evaluated for their potential anti-tyrosinase activity. Among them, compound 5l exhibited outstanding anti-tyrosinase activity with IC50 of 3.04 ± 0.01 μM compared to 14.13 ± 0.80 μM of kojic acid. Kinetic study revealed compound 5l to be a reversible and uncompetitive tyrosinase inhibitor. 3D fluorescence and CD spectra results showed treatment of compound 5l lead to the conformational changes of tyrosinase. Molecular docking revealed the binding between compound 5l and tyrosinase. Furthermore, compound 5l inhibited melanin content and cellular tyrosinase activity both in B16F10 cells and zebrafish model with no toxicity effect. Taken together, our findings suggested that compound 5l could be used as potential candidate to relieve tyrosinase-related hyperpigmentation.