title: Rational design, synthesis and structure-activity relationships of 4-alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues as novel tyrosinase inhibitors.
abstract: In continuing our program aimed to search for potent compounds as highly efficient tyrosinase inhibitors, here a series of novel 4-alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues were designed, synthesized and their biological activities on mushroom tyrosinase were evaluated. Notably, most of compounds displayed remarkable tyrosinase inhibitory activities with IC50 value of lower than 1.0μM. Furthermore, the structure-activity relationships (SARs) were discussed and the inhibition mechanism and the inhibitory kinetics of selected compounds 7k and 8d were also investigated. Taken together, these results suggested that such compounds could serve as the promising candidates for the treatment of tyrosinase-related disorders and further development of such compounds might be of great interest.
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors: Ao
authors: A
authors: You
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China; VARI/SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors: Jie
authors: J
authors: Zhou
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors: Senchuan
authors: S
authors: Song
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors: Guoxun
authors: G
authors: Zhu
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China. Electronic address: yjhxhc@mail.sysu.edu.cn.
authors: Huacan
authors: H
authors: Song
authors: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China; VARI/SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: yiwei2@mail2.sysu.edu.cn.
authors: Wei
authors: W
authors: Yi
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013882:Thiosemicarbazones; D014442:Monophenol Monooxygenase
keywords: 4-Alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues; Inhibition mechanism; Inhibitory kinetics; SARs; Tyrosinase inhibitor