title: Design, synthesis and biological evaluation of hydroxy- or methoxy-substituted 5-benzylidene(thio) barbiturates as novel tyrosinase inhibitors.
abstract: Here a new class of hydroxy- or methoxy-substituted 5-benzylidene(thio)barbiturates were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that several compounds had more potent tyrosinase inhibitory activities than the widely used tyrosinase inhibitor kojic acid (IC50=18.25μM). In particular, 3',4'-dihydroxylated 1e was found to be the most potent inhibitor with IC50 value of 1.52μM. The inhibition mechanism analysis revealed that the potential compounds 1e and 2e exhibited such inhibitory effects on tyrosinase by acting as the irreversible inhibitors. Structure-activity relationships' (SARs) analysis also suggested that further development of such compounds might be of interest.
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Cai
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
authors.forename: Dehai
authors.initials: D
authors.lastname: Mou
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center (Guangzhou), Building 34, 100 Xianlie Middle Road, Guangzhou 510070, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Pan
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wan
authors.affiliation: 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.forename: Huacan
authors.initials: H
authors.lastname: Song
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China. Electronic address: yiwei2@mail2.sysu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
mesh_terms: D000363:Agaricales / Q000201:enzymology; D001463:Barbiturates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001463:Barbiturates; D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase
keywords: 5-Benzylidene(thio)barbiturate; Inhibition mechanism; SARs; Tyrosinase inhibitor