title: Searching for indole derivatives as potential mushroom tyrosinase inhibitors.
abstract: Tyrosinase is a copper-containing enzyme widely distributed in nature, involved in the biosynthesis of melanin whose role is to protect the skin from ultraviolet damage. A great interest has been shown on the melanin involvement in malignant melanoma and other carcinogenetic processes. These phenomena have encouraged the research of tyrosinase inhibitors useful in therapeutic field as well as in foods and cosmetics to prevent browning. The idea was to screen our "in house" database to select suitable lead compounds for the discovery of potential drug-inhibiting enzyme. The obtained biological results demonstrated that compounds containing 4-fluorobenzyl moiety at N - 1 position of indole system showed the best activity. In addition, the role of the portion linked to the carbonyl group at C - 3 was discussed. A Lineweaver-Burk kinetic analysis of the most active indoles, CHI 1043 and derivative 4, showed a mixed-type inhibition in the presence of L-3,4-dihydroxyphenylalanine (L-DOPA) as substrate.
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.|b Fondazione Prof. Antonio Imbesi , Messina , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Certo
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Germanò
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rapisarda
authors.affiliation: a Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute , Università di Messina , Messina , Italy and.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D014442:Monophenol Monooxygenase
keywords: Indoles; kinetic analysis; synthesis; tyrosinase