Synthesis, human monoamine oxidase inhibitory activity and molecular docking studies of 3-heteroarylcoumarin derivatives

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Series of 3-indolyl and 3-thiophenylcoumarins were synthesized and evaluated as inhibitors of the two human MAO isoforms, hMAO-A and hMAO-B. In general, the derivatives were found to be selective hMAO-B...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2011-04, Vol.46 (4), p.1147-1152
Main Authors: Delogu, Giovanna, Picciau, Carmen, Ferino, Giulio, Quezada, Elías, Podda, Gianni, Uriarte, Eugenio, Viña, Dolores
Format: Article
Language:English
Subjects:
3-Heteroarylcoumarins
Biological and medical sciences
Coumarins - chemical synthesis
Coumarins - chemistry
Coumarins - metabolism
Coumarins - pharmacology
Humans
Medical sciences
Miscellaneous
Models, Molecular
Molecular docking
Monoamine Oxidase - chemistry
Monoamine Oxidase - metabolism
Monoamine Oxidase Inhibitors - chemical synthesis
Monoamine Oxidase Inhibitors - chemistry
Monoamine Oxidase Inhibitors - metabolism
Monoamine Oxidase Inhibitors - pharmacology
Monoamino oxidase (MAO)
Neuropharmacology
Perkin reaction
Pharmacology. Drug treatments
Protein Conformation
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Summary:Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Series of 3-indolyl and 3-thiophenylcoumarins were synthesized and evaluated as inhibitors of the two human MAO isoforms, hMAO-A and hMAO-B. In general, the derivatives were found to be selective hMAO-B inhibitors with IC 50 values in the nanoMolar (nM) to microMolar (μM) range. Docking experiments were carried out in order to compare the theoretical and experimental affinity of these compounds to the hMAO-B protein. According to our results, docking experiments could be an interesting approach to try to predict the activity of this class of coumarins against MAO-B receptors. Three series of 3-heteroarylcoumarin derivatives have been synthesized and evaluated as hMAO inhibitors. The biological data were compared to the molecular docking study. [Display omitted] ► Synthesis of 3-heteroarylcumarins. ► Evaluation of hMAO activity. ► Docking studies. ► Prediction of hMAO-B activity for new derivatives.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2011.01.033