A Novel Synthesized Tyrosinase Inhibitor: (E)-2-((2,4-Dihydroxyphenyl)diazenyl)phenyl 4-Methylbenzenesulfonate as an Azo-Resveratrol Analog

Abstract

We synthesized a novel series of (E)-2-((substituted phenyl)diazenyl)phenyl 4-methylbenzenesulfonate derivatives (2 and 3) and (E)-2-((substituted phenyl)diazenyl)phenol derivatives (4 and 5), and conducted an evaluation in order to determine their inhibitory effects on mushroom tyrosinase, with the aim of discovering a tyrosinase inhibitor. Most of the compounds (3–5) exhibited higher inhibitory effects than kojic acid (IC₅₀ = 49.08 µM), a representative tyrosinase inhibitor. A novel synthesized compound, (E)-2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate (3), showed the best results with an IC₅₀ of 17.85 µM, and showed competitive inhibition on Lineweaver-Burk plots, as further confirmed by the docking results. In addition, active compounds 3–5 were not cytotoxic to cultured B16F10 cells at the concentrations tested, and inhibited both tyrosinase and melanin synthesis. Therefore the active compounds (3–5) might be considered excellent candidates for use in the development of therapeutic agents for diseases associated with hyperpigmentation.