Versatile effects of aurone structure on mushroom tyrosinase activity.
Elucidation of the binding modes of Ty inhibitors is an important step for in-depth studies on how to regulate tyrosinase activity. In this paper we highlight the extraordinarily versatile effects of the aurone structure on mushroom Ty activity. Depending on the position of the OH group on the B-ring, aurones can behave either as substrates or as hyperbolic activators. The synthesis of a hybrid aurone through combination of an aurone moiety with HOPNO (2-hydroxypyridine N-oxide), a good metal chelate, led us to a new, efficient, mixed inhibitor for mushroom tyrosinase. Another important feature pointed out by our study is the presence of more than one site for aurone compounds on mushroom tyrosinase. Because study of the binding of the hybrid aurone was difficult to perform with the enzyme, we undertook binding studies with tyrosinase functional models in order to elucidate the binding mode (chelating vs. bridging) on a dicopper(II) center. Use of EPR combined with theoretical DFT calculations allowed us to propose a preferred chelating mode for the interaction of the hybrid aurone with a dicopper(II) center.
Institut des Sciences Moléculaires de Marseille, Équipe BiosCiences, UMR-CNRS 7313, Aix-Marseille Université Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France.
Carole
C
Dubois
Romain
R
Haudecoeur
Maylis
M
Orio
Catherine
C
Belle
Constance
C
Bochot
Ahcène
A
Boumendjel
Renaud
R
Hardré
Hélène
H
Jamet
Marius
M
Réglier
D000363:Agaricales / Q000201:enzymology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C547041:2-hydroxypyridine-N-oxide; D001572:Benzofurans; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D011725:Pyridines; C486837:aurone; D014442:Monophenol Monooxygenase