Synthesis and biological evaluation of unsymmetrical curcumin analogues as tyrosinase inhibitors

Yongfu Jiang, Zhiyun Du, Guihua Xue, Qian Chen, Yujing Lu, Xi Zheng, Allan H. Conney, Kun Zhang

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 (IC50 = 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.

Original languageEnglish (US)
Pages (from-to)3948-3961
Number of pages14
JournalMolecules
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2013

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All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Keywords

  • Biological evaluation
  • Inhibition kinetics
  • Synthesis
  • Tyrosinase inhibitors
  • Unsymmetrical curcumin analogues

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