title: Synthesis and biological evaluation of unsymmetrical curcumin analogues as tyrosinase inhibitors.
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 (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.
authors.affiliation: Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.forename: Guihua
authors.initials: G
authors.lastname: Xue
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Yujing
authors.initials: Y
authors.lastname: Lu
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D005260:Female; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059808:Polyphenols / Q000032:analysis / Q000138:chemical synthesis; D011753:Pyrones / Q000032:analysis; D012118:Resorcinols / Q000032:analysis; D023382:Toxicity Tests, Acute
chemical_list: C508220:4-n-butylresorcinol; D059808:Polyphenols; D011753:Pyrones; D012118:Resorcinols; C011890:kojic acid; D014442:Monophenol Monooxygenase; D003474:Curcumin
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