linezolid has been researched along with benzamide* in 2 studies
2 other study(ies) available for linezolid and benzamide
| Article | Year |
|---|---|
Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators.
Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. aureus. Further molecular biological studies and docking analyses proved that the compound functioned as an effective inhibitor to alter the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which finally terminated the cell division and caused cell death. Taken together, these results could suggest a promising chemotype for development of new FtsZ-targeting bactericidal agent. Topics: Anti-Bacterial Agents; Bacillus pumilus; Bacillus subtilis; Bacterial Proteins; Benzamides; Cell Survival; Cytoskeletal Proteins; Dose-Response Relationship, Drug; Drug Design; HeLa Cells; Humans; Isoxazoles; Microbial Sensitivity Tests; Molecular Structure; Staphylococcus aureus; Structure-Activity Relationship | 2018 |
Design, synthesis and structure-activity relationships of substituted oxazole-benzamide antibacterial inhibitors of FtsZ.
The design, synthesis and structure-activity relationships of a series of oxazole-benzamide inhibitors of the essential bacterial cell division protein FtsZ are described. Compounds had potent anti-staphylococcal activity and inhibited the cytokinesis of the clinically-significant bacterial pathogen Staphylococcus aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of S. aureus harbouring the glycine-to-alanine amino acid substitution at residue 196 of FtsZ which conferred resistance to previously reported inhibitors in the series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the pharmacokinetic properties by increasing metabolic stability and provided a mechanism for creating pro-drugs. Combining multiple substitutions based on the findings reported in this study has provided small-molecule inhibitors of FtsZ with enhanced in vitro and in vivo antibacterial efficacy. Topics: Anti-Bacterial Agents; Bacterial Proteins; Benzamides; Cytoskeletal Proteins; Dose-Response Relationship, Drug; Drug Design; Microbial Sensitivity Tests; Molecular Structure; Oxazoles; Staphylococcus aureus; Structure-Activity Relationship | 2014 |