MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins.
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Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L, Vina D
MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins.
Bioorg Med Chem Lett. 2011 Jul 15;21(14):4224-7. doi: 10.1016/j.bmcl.2011.05.074. Epub 2011 May 30.
- PubMed ID
- 21684743 [ View in PubMed]
- Abstract
With the aim of finding the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins (compounds 1-4) and 3-benzoylcoumarins (compounds 5-8). A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds, at six and eight positions of the coumarin moiety, respectively. The synthesized compounds 1-8 were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC(50)=1.35nM) showed higher inhibitory activity than the R-(-)-deprenyl (IC(50)=19.60nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Iproniazid Amine oxidase [flavin-containing] B IC 50 (nM) 7540 N/A N/A Details Selegiline Amine oxidase [flavin-containing] A IC 50 (nM) 67250 N/A N/A Details Selegiline Amine oxidase [flavin-containing] B IC 50 (nM) 19.6 N/A N/A Details