title: 2-Hydroxypyridine-N-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors.
abstract: With the aim to develop effective and selective human tyrosinase inhibitors, we investigated aurone derivatives whose B-ring was replaced by a non-oxidizable 2-hydroxypyridine-N-oxide (HOPNO) moiety. These aurones were synthesized and evaluated as inhibitors of purified human tyrosinase. Excellent inhibition activity was revealed and rationalized by theoretical calculations. The aurone backbone was especially found to play a crucial role, as the HOPNO moiety alone provided very modest activity on human tyrosinase. Furthermore, thein vitroactivity was confirmed by measuring the melanogenesis suppression ability of the compounds in melanoma cell lysates and whole cells. Our study reveals that HOPNO-embedded 6-hydroxyaurone is to date the most effective inhibitor of isolated human tyrosinase. Owing to its low toxicity and its high inhibition activity, it could represent a milestone on the path toward new valuable agents in dermocosmetics, as well as in medical fields where it was recently suggested that tyrosinase could play key roles.
authors.affiliation: Univ. Grenoble-Alpes/CNRS , DPM UMR 5063, CS 40700, 38058 Grenoble, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Haudecoeur
authors.affiliation: Department of Biology, University of Padova , Via Ugo Bassi 58b, Padova 35121, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Carotti
authors.affiliation: Univ. Grenoble-Alpes/CNRS , DCM UMR 5250, CS 40700, 38058 Grenoble, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gouron
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 , Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Maresca
authors.affiliation: Univ. Grenoble-Alpes/CNRS, DPM UMR 5063, CS 40700, 38058 Grenoble, France; Univ. Grenoble-Alpes/CNRS, DCM UMR 5250, CS 40700, 38058 Grenoble, France.
authors.forename: Elina
authors.initials: E
authors.lastname: Buitrago
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 , Marseille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Hardré
authors.affiliation: Department of Biology, University of Padova , Via Ugo Bassi 58b, Padova 35121, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bergantino
authors.affiliation: Univ. Grenoble-Alpes/CNRS , DCM UMR 5250, CS 40700, 38058 Grenoble, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jamet
authors.affiliation: Univ. Grenoble-Alpes/CNRS , DCM UMR 5250, CS 40700, 38058 Grenoble, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Belle
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 , Marseille, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Réglier
authors.affiliation: Department of Biology, University of Padova , Via Ugo Bassi 58b, Padova 35121, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bubacco
authors.affiliation: Univ. Grenoble-Alpes/CNRS , DPM UMR 5063, CS 40700, 38058 Grenoble, France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
keywords: Human tyrosinase; QM/MM calculations; aurones; human melanoma; transition state analogues