title: Synthesis and molecular modelling of novel substituted-4,5-dihydro-(1H)-pyrazole derivatives as potent and highly selective monoamine oxidase-A inhibitors.
abstract: This report describes novel pyrazoline derivatives investigated for their ability to selectively inhibit the activity of the A and B isoforms of monoamine oxidase. These new synthetic compounds proved to be reversible, potent, and selective inhibitors of monoamine oxidase-A rather than of monoamine oxidase-B, and are promising candidates to further advance drug discovery efforts. The most active compounds show inhibitory activity on monoamine oxidase-A in the 1.0x10(-8)-8.6x10(-9) M range. Moreover, it should be pointed out that for some compounds a high IC50>or=10(-9) M value is associated with a high A-selectivity (Selectivity Index monoamine oxidase-B/monoamine oxidase-A in the 10,000-12,500 range). Further insight to understand enzyme-inhibitor molecular interaction was obtained by docking experiments with the monoamine oxidase-A and monoamine oxidase-B isoforms.
authors.affiliation: Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi di Roma La Sapienza, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Fedele
authors.initials: F
authors.lastname: Manna
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Arianna
authors.initials: A
authors.lastname: Granese
authors.forename: Olivia
authors.initials: O
authors.lastname: Befani
authors.forename: Paola
authors.initials: P
authors.lastname: Turini
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase