Design and Synthesis of Hydroxypyridinone‑l‑phenylalanine Conjugates as Potential Tyrosinase Inhibitors

• Published in: Journal of agricultural and food chemistry 2013-07, Vol.61 (27), p.6597-6603
• Main Authors: Li, Dong-Fang, Hu, Pan-Pan, Liu, Mu-Song, Kong, Xiao-Le, Zhang, Jin-Chao, Hider, Robert C, Zhou, Tao
• Format: Article
• Language: English
• Subjects: Agaricales - chemistry; Agaricales - enzymology; Biological and medical sciences; cosmetics; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Food industries; food preservation; Fundamental and applied biological sciences. Psychology; Fungal Proteins - antagonists & inhibitors; Fungal Proteins - chemistry; inhibitory concentration 50; kojic acid; Molecular Structure; Monophenol Monooxygenase - antagonists & inhibitors; mushrooms; Phenylalanine - chemistry; Pyridones - chemistry; Pyrones - chemistry
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf401585f

A range of hydroxypyridinone-l-phenylalanine conjugates were synthesized starting from kojic acid. Their tyrosinase activity was determined, and it was found that one of the compounds ((S)-(5-(benzyloxy)-1-octyl-4-oxo-1,4-dihydropyridin-2-yl)­methyl 2-amino-3-phenylpropanoate, 5e) showed potent inhibitory effect against mushroom tyrosinase, the IC50 values for monophenolase and diphenolase activities being 12.6 and 4.0 μM, respectively. It was also demonstrated that these conjugates are mixed-type inhibitors, suggesting they could bind to both the free enzyme and the enzyme–substrate complexes. MTT assay indicated that 5e was nontoxic to three cell lines. This compound may find applications in food preservation and cosmetics.