文献类型：期刊文献

英文题名：Design and synthesis of thiourea derivatives with sulfur-containing heterocyclic scaffolds as potential tyrosinase inhibitors

作者：Liu, Pingping[1];Shu, Chen[1];Liu, Lujie[1];Huang, Qingchun[1];Peng, Yanqing[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

年份：2016

卷号：24

期号：8

起止页码：1866

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000372592900027)】；

基金：Financial support from National Key Technology R&D Program (2011BAE06B02) is gratefully acknowledged.

语种：英文

外文关键词：Tyrosinase; Inhibition; Thiourea derivatives; Thiadiazol; Thiophene

摘要：Tyrosinase is a key enzyme during the production of melanins in plants and animals. A class of novel N-aryl-N'-substituted phenylthiourea derivatives (3a-i, 6a-k) were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed some 4,5,6,7-tetrahydro-2-[[(phenylamino)thioxomethyl]amino]-benzo[b]thiophene-3-carboxylic acid derivatives (3a-i) exhibited moderate inhibitory potency on diphenolase activity of tyrosinase. When the scaffold of 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid was replaced with 2-(1,3,4-thiadiazol-2-yl)thio acetic acid, the inhibitory activity of compounds (6a-k) against tyrosinase was improved obviously; especially, the inhibitory activity of compound 6h (IC50 = 6.13 mu M) is significantly higher than kojic acid (IC50 = 33.3 mu M). Moreover, the analysis on inhibition mechanism revealed that compound 6h might plays the role as a noncompetitive inhibitor. (C) 2016 Elsevier Ltd. All rights reserved.