Inhibitory activity of novel kojic acid derivative containing trolox moiety on melanogenesis

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7466-9. doi: 10.1016/j.bmcl.2011.09.122. Epub 2011 Oct 17.

Abstract

A novel kojic acid derivative containing a trolox moiety, (±)-5-hydroxy-4-oxo-4H-pyran-2-yl methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (3a), was synthesized. The two biologically active compounds, namely, kojic acid and trolox, were conjugated via an ester bond as they are expected to behave synergistically. The antioxidant activity and the tyrosinase inhibitory activity of this novel kojic acid derivative on melanogenesis were evaluated. Compound 3a exhibited potent tyrosinase inhibitory activity and radical scavenging activity. Limited structure-activity relationship (SAR) investigations indicated that the tyrosinase inhibitory activities may originate from the kojic acid moiety, and the radical scavenging activity may be due to the phenolic hydroxyl group of trolox. Compound 3a also exhibited potent depigmenting activity in a cell-based assay. The limited SAR investigations revealed that the depigmenting activity of 3a may be due to the synergistic activities of kojic acid and its trolox moiety.

MeSH terms

  • Animals
  • Benzopyrans / chemical synthesis
  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology
  • Binding Sites
  • Cell Differentiation
  • Chromans / chemistry*
  • Computer Simulation
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Melanocytes / cytology
  • Melanocytes / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / metabolism*
  • Pyrones / chemical synthesis
  • Pyrones / chemistry*
  • Pyrones / pharmacology*
  • Structure-Activity Relationship

Substances

  • 5-hydroxy-4-oxo-4H-pyran-2-yl methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate
  • Benzopyrans
  • Chromans
  • Free Radical Scavengers
  • Pyrones
  • kojic acid
  • Monophenol Monooxygenase
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid