Design and synthesis of hydroxypyridinone-L-phenylalanine conjugates as potential tyrosinase inhibitors.

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.