Design, synthesis and biological evaluation of hydroxy- or methoxy-substituted 5-benzylidene (thio) barbiturates as novel tyrosinase inhibitors

被引：47

作者：

Chen, Zhiyong ^{[1
]}

Cai, Dachuan ^{[1
]}

Mou, Dehai ^{[1
]}

Yan, Qin ^{[2
]}

Sun, Yifeng ^{[1
]}

Pan, Wenlong ^{[1
]}

Wan, Yiqian ^{[2
]}

Song, Huacan ^{[2
]}

Yi, Wei ^{[2
]}

机构：

[1] China Natl Analyt Ctr Guangzhou, Guangdong Prov Publ Lab Anal & Testing Technol, Guangzhou 510070, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Sch Chem & Chem Engn, Guangzhou 510275, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 13期

关键词：

5-Benzylidene(thio)barbiturate; Tyrosinase inhibitor; SARs; Inhibition mechanism; MUSHROOM TYROSINASE; DERIVATIVES; RESVERATROL; ANALOGS; ACID; POLYPHENOLS; CHALCONES; STILBENES;

D O I：

10.1016/j.bmc.2014.04.060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 = 18.25 mu M). In particular, 3',4'-dihydroxylated 1e was found to be the most potent inhibitor with IC50 value of 1.52 mu M. 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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3279 / 3284

页数：6

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