Ester Derivatives of Kojic Acid and Polyphenols Containing Adamantane Moiety with Tyrosinase Inhibitory and Anti-inflammatory Properties

摘要

Nitric oxide (NO) is an important inflammatory mediator, synthesized by inducible nitric oxide synthase (iNOS). Over production of NO can lead to inflammatory diseases. Thus, much effort has been focused on finding potent inhibitors of NO production from natural sources or developing them by modifying natural products. Tyrosinase, a copper-containing enzyme, catalyzes two distinct reactions involved in melanin biosynthesis: hydroxylation of tyrosine to DOPA and oxidation of DOPA to dopaquinone. Three types of tyrosinase (met-, oxy-, and deoxytyrosinase) with different binuclear copper structures at the active site are involved. Kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) (1) is one of the metabolites used in fermentation by the species Aspergillus. Kojic acid inhibits tyrosinase via chelation to copper, which is necessary for tyrosinase inhibitory activity. Because of these effects, kojic acid has been used as a depigmentation agent in cosmetics and an antibrowning agent in food. Kojic acid has also been shown to scavenge free radicals and prevent photodamage.