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

作者：Liu, Pingping; Shu, Chen; Liu, Lujie; Huang, Qingchun; Peng, Yanqing^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(8): 1866-1871.

DOI：10.1016/j.bmc.2016.03.013

• Tyrosinase
• Inhibition
• Thiourea derivatives
• Thiadiazol
• Thiophene

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.

• 出版日期2016-4-15
• 单位华东理工大学