title: New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies.
abstract: 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.
authors.affiliation: Department of Life Science and Environment, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pintus
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal. Electronic address: mariacmatos@gmail.com.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Matos
authors.affiliation: CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hripcsak
authors.affiliation: CNC-IBILI, Pharmaceutical Chemistry Group, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Varela
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Pedro de Valdivia 425, 7500912 Santiago, Chile.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.affiliation: CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.affiliation: Department of Life Science and Environment, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Medda
authors.affiliation: Department of Life Science and Environment, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Di Petrillo
authors.affiliation: Department of Life Science and Environment, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Era
authors.affiliation: Department of Life Science and Environment, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fais
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013058:Mass Spectrometry; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D008543:Melanins; D014442:Monophenol Monooxygenase
keywords: 3-Heteroarylcoumarins; B16F10 melanoma cells; Melanogenesis; Tyrosinase inhibitors