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

6533b839fe1ef96bd12a5a52

RESEARCH PRODUCT

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

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

subject

Multidrug-resistant bacteria Clinical Biochemistry Antibiotics Drug Resistance Molecular Conformation Pharmaceutical Science Biochemistry chemistry.chemical_compound Antibiotics Drug Resistance Multiple Bacterial Drug Discovery Acetamides Side chain Oxadiazoles Absolute configuration Bacterial Stereoisomerism Hep G2 Cells BIO/10 - BIOCHIMICA 23S Anti-Bacterial Agents Molecular Docking Simulation RNA Ribosomal 23S Drug design Linezolid Antibiotics Multidrug-resistant bacteria Enantiomers Molecular Medicine Antibacterial activity Multiple Methicillin-Resistant Staphylococcus aureus Staphylococcus aureus medicine.drug_class Stereochemistry Cell Survival Microbial Sensitivity Tests Gram-Positive Bacteria Drug design medicine Humans Molecular Biology Oxazolidinones Ribosomal Binding Sites Organic Chemistry Antibiotic Linezolid Settore CHIM/06 - Chimica Organica Settore CHIM/08 - Chimica Farmaceutica Multiple drug resistance chemistry Enantiomers MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA Linezolid RNA Nucleic Acid Conformation Enantiomer Chirality (chemistry)

description

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.

year	journal	country	edition	language
2014-01-01	Bioorganicmedicinal chemistry

10.1016/j.bmc.2014.10.037 https://pubmed.ncbi.nlm.nih.gov/25464880