Synthesis and study of new hydroxylated biphenol derivatives as potential tyrosinase inhibitors

The role of melanin is to protect the skin from ultraviolet (UV) damage by absorbing UV sunlight Melanin is one of the most widely distributed pigments and is found in bacteria, fungi, plants and insects. Tyrosinase (polyphenol oxidase, E.C. 1.14.18.1) and laccase (phenol oxidase, E.C. 1.10.3.2) are, the keys enzymes in melanin biosynthesis, These inhibitors are also known to be useful in cosmetics as whitening agents.a The involvement of laccase in cuticle sclerotization or tanning is essential to insect survival.b Among the compounds recently studied the 4,4'-dihydroxybiphenyl 1 has been shown to be a potent inhibitor of tyrosinase.c Hydroxylated biphenyls with a C2-symmetry axis have attracted considerable interest because of the biological activity exerted by a number of natural occurring compounds containing this moiety.d Our study is aimed to prepare new biphenol derivatives as potential inhibitors of melanin production starting from compound 1. In the figure are reported some of the new synthesized biphenyls in which, with the aim to improve water-solubility, one hydroxyl is substituted by a aminoacid (2) gallic acid (3) and sugar (4 and 5) unit, respectively. Compounds 6-8 belong to the class of C-prenylated biphenyls. Biological evaluation on PC12 cells, phytoiatric tests and docking studies of the new derivatives were carried on.