New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies

Publication date: 1 March 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 5
Author(s): Francesca Pintus, Maria J. Matos, Santiago Vilar, George Hripcsak, Carla Varela, Eugenio Uriarte, Lourdes Santana, Fernanda Borges, Rosaria Medda, Amalia Di Petrillo, Benedetta Era, Antonella Fais
Melanogenesis is a physiological pathway for the formation of melanin. Tyrosinase catalyzes the first step of this process and down-regulation of its activity is responsible for the inhibition of melanogenesis. The search for molecules capable of controlling hyperpigmentation is a trend topic in health and cosmetics. A series of heteroarylcoumarins have been synthesized and evaluated. Compounds 4 and 8 exhibited higher tyrosinase inhibitory activities (IC50=0.15 and 0.38μM, respectively), than the reference compound, kojic acid (IC50=17.9μM). Compound 4 acts as competitive, while compound 8 as uncompetitive inhibitor of mushroom tyrosinase. Furthermore, compounds 2 and 8 inhibited tyrosinase activity and melanin production in B16F10 cells. In addition, compounds 2–4 and 8 proved to have an interesting antioxidant profile in both ABTS and DPPH radicals scavenging assays. Docking experiments were carried out in order to study the interactions between these heteroarylcoumarins and mushroom tyrosinase.

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