Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Melanoma Therapy

Tyrosinase is a key enzyme in melanogenesis, playing an important role in skin, hair, and eye pigmentation, as well as in the enzymatic browning of fruits and vegetables. Excessive tyrosinase activity leads to hyperpigmentation and other dermatological problems, and also causes losses in the food industry. For this reason, tyrosinase inhibitors have become the subject of intensive research in medicine, cosmetology, and food technology. Among the various inhibitors, compounds containing ketone and hydroxyl groups draw special attention, because they have the ability to chelate copper ions in the active center of enzyme or block an access to it.. This article discusses the possible mechanisms of action, based on molecular modeling of interaction of pdb database retrieved model of enzyme with known natural inhibitors – kojic acid and tropolone as well as newly synthesized and tested 6-hydroxyimino derivatives of imidazo[1,2-a]imidazole-5-ones. Results suggest that model of enzyme-ligand interaction can be useful in establishing affinity to tyrosinase of new natural and synthetic inhibitors. They can have broad applications in various fields, including melanoma therapy, and prospects for further development.