A novel synthesized tyrosinase inhibitor: (E)-2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate as an azo-resveratrol analog

Biosci Biotechnol Biochem. 2013;77(1):65-72. doi: 10.1271/bbb.120547. Epub 2013 Jan 7.

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 (IC(50) = 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 IC(50) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azo Compounds / chemical synthesis*
  • Azo Compounds / pharmacology
  • Benzenesulfonates / chemical synthesis*
  • Benzenesulfonates / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Assays
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors*
  • Fungal Proteins / metabolism
  • Kinetics
  • Melanins / antagonists & inhibitors*
  • Melanins / metabolism
  • Melanoma, Experimental / metabolism
  • Mice
  • Molecular Docking Simulation
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Pigmentation Disorders / drug therapy
  • Pyrones / pharmacology
  • Resveratrol
  • Stilbenes / chemistry*

Substances

  • 2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate
  • Azo Compounds
  • Benzenesulfonates
  • Enzyme Inhibitors
  • Fungal Proteins
  • Melanins
  • Pyrones
  • Stilbenes
  • kojic acid
  • Monophenol Monooxygenase
  • Resveratrol