New isoxazolidinone and 3,4-dehydro-ß-proline derivatives as antibacterial agents and MAO-inhibitors: A complex balance between two activities.
Eur J Med Chem
; 124: 906-919, 2016 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-27676470
ABSTRACT
Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, induces in many cases loss of selectivity as a major concern. A small library of compounds based on isoxazolidinone and dehydro-ß-proline scaffold was designed with the aim to obtain antibacterial agents, evaluating at the same time the potential effects of structural features on MAO inhibitory behaviour. The structural modification introduced in the backbone, starting from Linezolid model, lead to a significant loss in antibiotic activity, while a promising inhibitory effect could be observed on monoamino oxidases. These interesting results are also in agreement with docking experiments suggesting a good binding pose of the synthesized compounds into the pocket of the oxidase enzymes, in particular of MAO-B.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prolina
/
Antibacterianos
/
Inibidores da Monoaminoxidase
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article