Evaluation of dihydropyrimidin-(2 H)-one analogues and rhodanine derivatives as tyrosinase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 8; pp. 2376 - 2379
• Main Authors: Liu, Jinbing, Wu, Fengyan, Chen, Lingjuan, Hu, Jianming, Zhao, Liangzhong, Chen, Changhong, Peng, Liwang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.04.2011; Elsevier
• Subjects: Agaricales - enzymology; Analytical, structural and metabolic biochemistry; Biological and medical sciences; catechol oxidase; Dihydropyrimidin-(2 H)-one; enzyme inhibitors; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Inhibition mechanism; inhibitory concentration 50; Medical sciences; Miscellaneous; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; mushrooms; Oxidoreductases; Pharmacology. Drug treatments; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Rhodanine; Rhodanine - analogs & derivatives; Rhodanine - chemical synthesis; Rhodanine - pharmacology; Thiazolidinediones - chemical synthesis; Thiazolidinediones - chemistry; Thiazolidinediones - pharmacology; Thiones - chemical synthesis; Thiones - chemistry; Thiones - pharmacology; Tyrosinase inhibitors; Rhodanine; Tyrosinase inhibitors; Dihydropyrimidin-(2 H)-one; Inhibition mechanism; Sulfur nitrogen heterocycle; Five membered ring; Enzyme; Benzene derivatives; Enzyme inhibitor; Dihydropyrimidin-(2H)-one; Monophenol monooxygenase; In vitro; Mechanism; Structure activity relation; Oxidoreductases; Diether; Chemical synthesis; Thiazolidine derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.02.076

Compound 15 exhibited most potent tyrosinase inhibitory activity with IC 50 value of 0.56 mM. The inhibition mechanism analysis of compound 15 demonstrated that the inhibitory effect of the compound on the tyrosinase was irreversible. A series of dihydropyrimidin-(2 H)-one analogues and rhodanine derivatives were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant inhibitory activities. Especially, compound 15 bearing a hydroxyethoxyl group at position-4 of phenyl ring exhibited most potent tyrosinase inhibitory activity with IC 50 value of 0.56 mM. The inhibition mechanism analysis of compound 15 demonstrated that the inhibitory effect of the compound on the tyrosinase was irreversible. These results suggested that such compounds might be served as lead compounds for further designing new potential tyrosinase inhibitors.