Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.

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Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Alcaro S, Ortuso F, Yanez M, Orallo F, Cirilli R, Ferretti R, La Torre F

Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.

J Med Chem. 2008 Aug 28;51(16):4874-80. doi: 10.1021/jm800132g. Epub 2008 Jul 31.

PubMed ID
18666768 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ClorgilineAmine oxidase [flavin-containing] AIC 50 (nM)4460N/AN/ADetails
IproniazidAmine oxidase [flavin-containing] BIC 50 (nM)7540N/AN/ADetails
MoclobemideAmine oxidase [flavin-containing] AIC 50 (nM)361380N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] AIC 50 (nM)67250N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)19.6N/AN/ADetails