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Synthesis and Biological Evaluation of Unsymmetrical Curcumin Analogues as Tyrosinase Inhibitors
Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China
Department of Chemistry, Zhejiang Normal University, Jinhua 321004, China
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
* Authors to whom correspondence should be addressed.
Received: 31 January 2013; in revised form: 14 March 2013 / Accepted: 22 March 2013 / Published: 3 April 2013
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.
Keywords: unsymmetrical curcumin analogues; synthesis; tyrosinase inhibitors; biological evaluation; inhibition kinetics
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Jiang, Y.; Du, Z.; Xue, G.; Chen, Q.; Lu, Y.; Zheng, X.; Conney, A.H.; Zhang, K. Synthesis and Biological Evaluation of Unsymmetrical Curcumin Analogues as Tyrosinase Inhibitors. Molecules 2013, 18, 3948-3961.
Jiang Y, Du Z, Xue G, Chen Q, Lu Y, Zheng X, Conney AH, Zhang K. Synthesis and Biological Evaluation of Unsymmetrical Curcumin Analogues as Tyrosinase Inhibitors. Molecules. 2013; 18(4):3948-3961.
Jiang, Yongfu; Du, Zhiyun; Xue, Guihua; Chen, Qian; Lu, Yujing; Zheng, Xi; Conney, Allan H.; Zhang, Kun. 2013. "Synthesis and Biological Evaluation of Unsymmetrical Curcumin Analogues as Tyrosinase Inhibitors." Molecules 18, no. 4: 3948-3961.