title: Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.
abstract: A series of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones have been investigated for their ability to inhibit selectively the activity of the human A and B isoforms of monoamine oxidase (MAO). The target compounds, which present a stereogenic center on the cyclohexane ring, were obtained as pure (R) and (S) enantiomers by enantioselective HPLC. The absolute configuration of homochiral forms isolated on a semipreparative scale was obtained by a combined strategy based on chemical correlation and single-crystal X-ray diffraction. All compounds showed higher activity against the human MAO-B isoform with IC50 values ranging between 26.81 +/- 2.74 microM and 14.20 +/- 0.26 nM, and the assays carried out on the pure enantiomers showed higher activity for the (R) form. A computational study was performed by molecular mechanics, DFT-based quantomechanics, and docking techniques on the most active and human MAO-B selective inhibitor 8.
authors.affiliation: Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Elias
authors.initials: E
authors.lastname: Maccioni
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Arianna
authors.initials: A
authors.lastname: Granese
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Francisco
authors.initials: F
authors.lastname: Orallo
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Rosella
authors.initials: R
authors.lastname: Ferretti
authors.forename: Francesco
authors.initials: F
authors.lastname: La Torre
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000737:chemistry; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013816:Thermodynamics; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000737:chemistry
chemical_list: C527963:2-methylcyclohexanone thiosemicarbazone; D003512:Cyclohexanones; D006835:Hydrazones; D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D013882:Thiosemicarbazones; D008995:Monoamine Oxidase