title: Action of 2,2',4,4'-tetrahydroxybenzophenone in the biosynthesis pathway of melanin.
abstract: 2,2',4,4'-tetrahydroxybenzophenone (Uvinul D50), a sunscreen used in cosmetics, has two effects in the melanin biosynthesis pathway. On the one hand, it acts a weak inhibitor of tyrosinase and on the other, it accelerates the conversion of dopachrome to melanin. Uvinul D50 was seen to behave as a weak competitive inhibitor: apparent constant inhibition=2.02±0.09mM and IC50=3.82±0.39mM established in this work. These values are higher than those in the bibliography, which tend to be undersetimated. This discrepancy could be explained by the reaction of Uvinul D50 with the dopachrome produced from l-tyrosine or l-dopa, which would interfere in the measurement. Based on studies of its docking to tyrosinase, it seems that Uvinul D50 interacts with the active site of the enzyme (oxytyrosinase) both in its protonated and deprotonated forms (pKa=7). However, it cannot be hydroxylated, meaning that it acts as a weak inhibitor, not as an alternative substrate, despite its resorcinol structure. Uvinul D50 can be used as sunscreen, in low concentrations without significant adverse effects on melanogenesis.
authors.affiliation: GENZ-Group of Research on Enzymology(1), Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Espinardo, Murcia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Jimenez
authors.affiliation: Group of Molecular Interactions in Membranes, Department of Biochemistry and Molecular Biology-A, University of Murcia, E-30100, Espinardo, Murcia, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Teruel-Puche
authors.affiliation: University of Murcia, Faculty of Veterinary, Group of Chemistry of Carbohydrates, Industrial Polymers and Additives, Department of Organic Chemistry, 30100 Murcia, Spain.
authors.forename: Pedro Antonio
authors.initials: PA
authors.lastname: Garcia-Ruiz
authors.affiliation: Group of Synthetic Organic Chemistry, Department of Organic Chemistry, Faculty of Chemistry, University of Murcia, E-30100, Espinardo, Murcia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Berna
authors.affiliation: GENZ-Group of Research on Enzymology(1), Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Espinardo, Murcia, Spain.
authors.forename: Jose Neptuno
authors.initials: JN
authors.lastname: Rodríguez-López
authors.affiliation: GENZ-Group of Research on Enzymology(1), Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Espinardo, Murcia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Tudela
authors.affiliation: GENZ-Group of Research on Enzymology(1), Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Espinardo, Murcia, Spain. Electronic address: canovasf@um.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Canovas
mesh_terms: D001577:Benzophenones / Q000737:chemistry* / Q000627:therapeutic use; D053898:Biosynthetic Pathways; D006801:Humans; D045563:Indolequinones / Q000737:chemistry / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis* / Q000737:chemistry; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D013473:Sunscreening Agents / Q000737:chemistry* / Q000627:therapeutic use; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001577:Benzophenones; D045563:Indolequinones; D008543:Melanins; D013473:Sunscreening Agents; C001123:dopachrome; D014443:Tyrosine; D014442:Monophenol Monooxygenase; C035476:2,2',4,4'-tetrahydroxybenzophenone
keywords: 2,2′,4,4′-tetrahydroxybenzophenonee; Inhibitor; Kinetics; Tyrosinase; Uvinul D50