Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives.

Article Details

Citation

Secci D, Carradori S, Bolasco A, Chimenti P, Yanez M, Ortuso F, Alcaro S

Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives.

Eur J Med Chem. 2011 Oct;46(10):4846-52. doi: 10.1016/j.ejmech.2011.07.017. Epub 2011 Jul 19.

PubMed ID
21872365 [ View in PubMed
]
Abstract

Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC(50) values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.

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
IsatinAmine oxidase [flavin-containing] BIC 50 (nM)18750N/AN/ADetails
MoclobemideAmine oxidase [flavin-containing] AIC 50 (nM)361380N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] AIC 50 (nM)67.25N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)19.6N/AN/ADetails