New potent antibacterials against Gram-positive multiresistant pathogens: Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles

Cosimo G. Fortuna, Roberto Berardozzi, Carmela Bonaccorso, Gianluigi Caltabiano, Lorenzo Di Bari, Laura Goracci, Annalisa Guarcello, Andrea Pace, Antonio Palumbo Piccionello, Gennaro Pescitelli, Paola Pierro, Elena Lonati, Alessandra Bulbarelli, Clementina E A Cocuzza, Giuseppe Musumarra, Rosario Musumeci

Research output: Contribution to journalArticle

Abstract

The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistant linezolid bacterial strains was higher than that of linezolid.

Original languageEnglish
Pages (from-to)6814-6825
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number24
DOIs
Publication statusPublished - Dec 15 2014

Fingerprint

Linezolid
Oxadiazoles
Chirality
Pathogens
Oxazolidinones
Molecular modeling
Enantiomers

Keywords

  • Antibiotics
  • Drug design
  • Enantiomers
  • Linezolid
  • Multidrug-resistant bacteria

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

New potent antibacterials against Gram-positive multiresistant pathogens : Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles. / Fortuna, Cosimo G.; Berardozzi, Roberto; Bonaccorso, Carmela; Caltabiano, Gianluigi; Di Bari, Lorenzo; Goracci, Laura; Guarcello, Annalisa; Pace, Andrea; Palumbo Piccionello, Antonio; Pescitelli, Gennaro; Pierro, Paola; Lonati, Elena; Bulbarelli, Alessandra; Cocuzza, Clementina E A; Musumarra, Giuseppe; Musumeci, Rosario.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 24, 15.12.2014, p. 6814-6825.

Research output: Contribution to journalArticle

Fortuna, CG, Berardozzi, R, Bonaccorso, C, Caltabiano, G, Di Bari, L, Goracci, L, Guarcello, A, Pace, A, Palumbo Piccionello, A, Pescitelli, G, Pierro, P, Lonati, E, Bulbarelli, A, Cocuzza, CEA, Musumarra, G & Musumeci, R 2014, 'New potent antibacterials against Gram-positive multiresistant pathogens: Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles', Bioorganic and Medicinal Chemistry, vol. 22, no. 24, pp. 6814-6825. https://doi.org/10.1016/j.bmc.2014.10.037
Fortuna, Cosimo G. ; Berardozzi, Roberto ; Bonaccorso, Carmela ; Caltabiano, Gianluigi ; Di Bari, Lorenzo ; Goracci, Laura ; Guarcello, Annalisa ; Pace, Andrea ; Palumbo Piccionello, Antonio ; Pescitelli, Gennaro ; Pierro, Paola ; Lonati, Elena ; Bulbarelli, Alessandra ; Cocuzza, Clementina E A ; Musumarra, Giuseppe ; Musumeci, Rosario. / New potent antibacterials against Gram-positive multiresistant pathogens : Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 24. pp. 6814-6825.
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