title: Design and synthesis of thiourea derivatives with sulfur-containing heterocyclic scaffolds as potential tyrosinase inhibitors.
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 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.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Lujie
authors.initials: L
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: yqpeng@ecust.edu.cn.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Peng
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry* / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D013455:Sulfur; D014442:Monophenol Monooxygenase; D013890:Thiourea
keywords: Inhibition; Thiadiazol; Thiophene; Thiourea derivatives; Tyrosinase