Design and synthesis of thiourea derivatives with sulfur-containing heterocyclic scaffolds as potential tyrosinase inhibitors. Issue 8 (15th April 2016)

• Record Type: Journal Article
• Authors: Liu, Pingping; Shu, Chen; Liu, Lujie; Huang, Qingchun; Peng, Yanqing
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 8(2016)
• Page Start: 1866
• Page End: 1871
• Publication Date: 2016-04-15
• Subjects: Tyrosinase -- Inhibition -- Thiourea derivatives -- Thiadiazol -- Thiophene; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.03.013
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 compound6h (IC50 = 6.13 μM) is significantly higher than kojic acid (IC50 = 33.3 μM). Moreover, the analysis on inhibition mechanism revealed that compound6h might plays the role as a noncompetitive inhibitor.