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

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• 作者：Pingping Liu ; Chen Shu ; Lujie Liu ; Qingchun Huang ; Yanqing Peng ; ^{yqpeng@ecust.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tyrosinase ; Inhibition ; Thiourea derivatives ; Thiadiazol ; Thiophene
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：24
• 期：8
• 页码：1866-1871
• 全文大小：703 K

文摘

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 μM) is significantly higher than kojic acid (IC₅₀ = 33.3 μM). Moreover, the analysis on inhibition mechanism revealed that compound 6h might plays the role as a noncompetitive inhibitor.