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-β-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.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Ferrazzano L,Viola A,Lonati E,Bulbarelli A,Musumeci R,Cocuzza C,Lombardo M,Tolomelli Adoi
10.1016/j.ejmech.2016.09.007subject
Has Abstractpub_date
2016-11-29 00:00:00pages
906-919eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30735-8journal_volume
124pub_type
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