Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors.
A series of 3,5-diaryl pyrazoles were prepared and assayed for their ability to inhibit reversibly monoamine oxidase-A (MAO-A) and monoamine oxidase B (MAO-B). Several compounds show inhibitory activity with concentration values in the nanomolar range. A computational work was carried out on the two most selective inhibitors that have tautomeric pyrazole forms. The binding free energies of these compounds for each MAO isoform were influenced by the tautomeric equilibria.
Chimenti
Franco
F
Dip. di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università di Roma "La Sapienza", P.le Aldo Moro, 5, 00185 Rome, Italy.
Fioravanti
Rossella
R
Bolasco
Adriana
A
Manna
Fedele
F
Chimenti
Paola
P
Secci
Daniela
D
Befani
Olivia
O
Turini
Paola
P
Ortuso
Francesco
F
Alcaro
Stefano
S
D007527:Isoenzymes / Q000737:chemistry; D007536:Isomerism; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase