2-Hydroxypyridine-N-oxide-Embedded Aurones as Potent Human Tyrosinase Inhibitors  
[Full paper ]
R. Haudecoeur, M. Carotti, A. Gouron, M. Maresca, E. Buitrago, R. Hardré, E. Bergantino, H. Jamet, C. Belle, M. Réglier, L. Bubacco, A. Boumendjel
ACS Med. Chem. Lett. 2017, 8, 55-60.
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, the in vitro activity 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.