Synthesis and biological evaluation of unsymmetrical curcumin analogues as tyrosinase inhibitors

Molecules. 2013 Apr 3;18(4):3948-61. doi: 10.3390/molecules18043948.


Synthesis and biological evaluation of unsymmetrical curcumin analogues (UCAs) have been achieved. Tyrosinase inhibitory activities were found for most of the prepared synthetic UCAs. Among them, compounds containing 4-hydroxyl-substituted phenolic rings with C-2/C-4- or C-3/C-4-dihydroxyl-substituted diphenolic rings were more active (IC(50) = 1.74~16.74 μM) than 4-butylresorcinol and kojic acid, which suggested that the 4-hydroxyl groups in UCAs play a crucial role in tyrosinase inhibitory activities. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed compounds 3c and 3i containing catecholic rings were mixed-competitive inhibitors, whereas compounds 3d and 3j containing resorcinolic rings were competitive inhibitors. The preliminary evaluation results of acute toxicity showed the representative 3d and 3j were non-toxic in mice dosed at 1,200 mg/kg. This research suggests that, with the advantage of being readily prepared small molecules, polyphenolic UCAs have the potential to develop into pharmacological inhibitors of tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis*
  • Female
  • Inhibitory Concentration 50
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Polyphenols / analysis
  • Polyphenols / chemical synthesis
  • Pyrones / analysis
  • Resorcinols / analysis
  • Toxicity Tests, Acute


  • 4-n-butylresorcinol
  • Polyphenols
  • Pyrones
  • Resorcinols
  • kojic acid
  • Monophenol Monooxygenase
  • Curcumin