Novel coumarin derivatives as potential tyrosinase inhibitors: Synthesis, binding analysis and biological evaluation

A novel series of thirty coumarin derivatives (4a ti r, 5a -l) constituted by coumarin and cinnamic acid/benzoic acid through oxime linkage were synthesized and evaluated for their poten-tial anti-tyrosinase activity. Among them, compound 5l exhibited outstanding anti-tyrosinase activ-ity with IC50 of 3.04 +/- 0.01 lM compared to 14.13 +/- 0.80 lM 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, com-pound 5l inhibited melanin content and cellular tyrosinase activity both in B16F10 cells and zebra -fish model with no toxicity effect. Taken together, our findings suggested that compound 5l could be used as potential candidate to relieve tyrosinase-related hyperpigmentation.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).