title: New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.
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.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy. Electronic address: cg.fortuna@unict.it.
authors.forename: Cosimo G
authors.initials: CG
authors.lastname: Fortuna
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento, 35, I-56126 Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Berardozzi
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Bonaccorso
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Caltabiano
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento, 35, I-56126 Pisa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Bari
authors.affiliation: Laboratory for Chemometrics and Cheminformatics, Chemistry Department, University of Perugia, Via Elce di Sotto 10, I-06123 Perugia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Goracci
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze Ed. 17-Parco D'Orleans II, I-90128 Palermo, Italy; Istituto EuroMediterraneo di Scienza e Tecnologia (IEMEST), Via Emerico Amari 123, I-90139 Palermo, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guarcello
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze Ed. 17-Parco D'Orleans II, I-90128 Palermo, Italy; Istituto EuroMediterraneo di Scienza e Tecnologia (IEMEST), Via Emerico Amari 123, I-90139 Palermo, Italy. Electronic address: andrea.pace@unipa.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze Ed. 17-Parco D'Orleans II, I-90128 Palermo, Italy; Istituto EuroMediterraneo di Scienza e Tecnologia (IEMEST), Via Emerico Amari 123, I-90139 Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo Piccionello
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento, 35, I-56126 Pisa, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pescitelli
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze Ed. 17-Parco D'Orleans II, I-90128 Palermo, Italy; Istituto EuroMediterraneo di Scienza e Tecnologia (IEMEST), Via Emerico Amari 123, I-90139 Palermo, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pierro
authors.affiliation: Dipartimento di Scienze della Salute, Università di Milano-Bicocca, Via Cadore 48, I-20900 Monza (MB), Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Lonati
authors.affiliation: Dipartimento di Scienze della Salute, Università di Milano-Bicocca, Via Cadore 48, I-20900 Monza (MB), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bulbarelli
authors.affiliation: Dipartimento di Chirurgia e Medicina Traslazionale, Università di Milano-Bicocca, Via Cadore 48, I-20900 Monza (MB), Italy.
authors.forename: Clementina E A
authors.initials: CE
authors.lastname: Cocuzza
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumarra
authors.affiliation: Dipartimento di Chirurgia e Medicina Traslazionale, Università di Milano-Bicocca, Via Cadore 48, I-20900 Monza (MB), Italy. Electronic address: rosario.musumeci@unimib.it.
authors.forename: Rosario
authors.initials: R
authors.lastname: Musumeci
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023303:Oxazolidinones / Q000737:chemistry* / Q000494:pharmacology; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D010069:Oxadiazoles; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid
keywords: Antibiotics; Drug design; Enantiomers; Linezolid; Multidrug-resistant bacteria