New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens.

Annalisa Guarcello, Andrea Pace, Antonio Palumbo Piccionello, Gianluigi Caltabiano, Annalisa Guarcello, Andrea Pace, Carmela Bonaccorso, Giuseppe Musumarra, Paola Pierro, Alessandra Bulbarelli, Laura Goracci, Cosimo G. Fortuna, Clementina E. A. Cocuzza, Laura Rizzi, Rosario Musumeci, Antonio Palumbo Piccionello, Paola Pierro

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31 Citations (Scopus)

Abstract

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported.Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activityagainst Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or evensuperior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) sidechainare required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity butits presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using twodifferent approaches e FLAP and Amber software e shows that in the binding pose of the newly synthesizedcompounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazolemoiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interactionwith U2585 is retained.
Original languageEnglish
Pages (from-to)533-545
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume65
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Guarcello, A., Pace, A., Palumbo Piccionello, A., Caltabiano, G., Guarcello, A., Pace, A., Bonaccorso, C., Musumarra, G., Pierro, P., Bulbarelli, A., Goracci, L., Fortuna, C. G., Cocuzza, C. E. A., Rizzi, L., Musumeci, R., Piccionello, A. P., & Pierro, P. (2013). New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens. European Journal of Medicinal Chemistry, 65, 533-545.