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

[Display omitted] 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...

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Published in:Bioorganic & medicinal chemistry 2017-03, Vol.25 (5), p.1687-1695
Main Authors: Pintus, Francesca, Matos, Maria J., Vilar, Santiago, Hripcsak, George, Varela, Carla, Uriarte, Eugenio, Santana, Lourdes, Borges, Fernanda, Medda, Rosaria, Di Petrillo, Amalia, Era, Benedetta, Fais, Antonella
Format: Article
Language:English
Subjects:
3-Heteroarylcoumarins
Animals
Antioxidants - pharmacology
B16F10 melanoma cells
Carbon-13 Magnetic Resonance Spectroscopy
Cell Line, Tumor
Enzyme Inhibitors - pharmacology
Mass Spectrometry
Melanins - antagonists & inhibitors
Melanins - biosynthesis
Melanogenesis
Mice
Models, Molecular
Molecular Docking Simulation
Monophenol Monooxygenase - antagonists & inhibitors
Proton Magnetic Resonance Spectroscopy
Tyrosinase inhibitors
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Summary:[Display omitted] 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2017.01.037