Biomedical applications of tyrosinases and tyrosinase inhibitors.

Tyrosinase is involved in several human diseases, among which hypopigmentation and depigmentation conditions (vitiligo, idiopathic guttate hypomelanosis, pityriasis versicolor, pityriasis alba) and hyperpigmentations (melasma, lentigines, post-inflammatory and periorbital hyperpigmentation, cervical idiopathic poikiloderma and acanthosis nigricans). There are increasing evidences that tyrosinase plays a relevant role in the formation and progression of melanoma, a difficult to treat skin tumor. Hydroquinone, azelaic acid and tretinoin (all-trans-retinoic acid) are clinically used in the management of some hyperpigmentations, whereas many novel chemotypes acting as tyrosinase inhibitors with potential antimelanoma action are being investigated. Kojic acid, hydroquinone, its glycosylated derivative arbutin, or the resorcinol derivative rucinol are used in cosmesis in creams as skin whitening agents, whereas no antimelanoma tyrosinase inhibitor reached clinical trials so far, although thiamidol is a recently approved new tyrosinase inhibitor for the treatment of melasma. Kojic acid and vitamin C are used for avoiding vegetable/food oxidative browning due to the tyrosinase-catalyzed reactions, whereas bacterial enzymes show potential in biotechnological applications, for the production of mixed melanins, for protein cross-linking reactions, for producing phenol(s) biosensors, of for the production of L-DOPA, an anti-Parkinson's disease drug.