Tricyclic Benzo[1,3]oxazinyloxazolidinones as Potent Antibacterial Agents against Drug-Resistant Pathogens.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Washington Dc : American Chemical Society
      Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
    • Subject Terms:
      Anti-Bacterial Agents*/pharmacology ; Anti-Bacterial Agents*/chemical synthesis ; Anti-Bacterial Agents*/chemistry ; Microbial Sensitivity Tests* ; Oxazolidinones*/pharmacology ; Oxazolidinones*/chemical synthesis ; Oxazolidinones*/chemistry ; Biofilms*/drug effects ; Methicillin-Resistant Staphylococcus aureus*/drug effects; Animals ; Mice ; Structure-Activity Relationship ; Drug Resistance, Bacterial/drug effects ; Linezolid/pharmacology ; Linezolid/chemical synthesis
    • Abstract:
      Herein, we developed a series of benzo[1,3]oxazinyloxazolidinones as potent antibacterial agents. Some of the compounds exhibited potent antibacterial activity against a range of clinical drug-resistant pathogens, including Mtb, MRSA, MRSE, VISA, and VRE. Notably, compound 16d inhibited protein synthesis and displayed potent activity against linezolid-resistant Enterococcus faecalis . Although 16d showed cross-resistance to linezolid-resistant MRSA, the frequency of resistance development of MRSA against 16d was lower compared to that of linezolid. Additionally, 16d exhibited excellent pharmacokinetic properties and superior in vivo efficacy compared to linezolid. Furthermore, compound 16d modulated cytokine levels and ameliorated histopathological changes in major organs of bacterially infected mice. Hoechst-PI double staining and scanning electron microscopy analyses revealed that 16d exhibited some similarities with linezolid in its effects while also demonstrating a distinct mechanism characterized by cell membrane damage. Moreover, 16d significantly disrupted the MRSA biofilms. The antibacterial agent 16d represents a promising candidate for the treatment of serious infections caused by drug-resistant bacteria.
    • Accession Number:
      0 (Anti-Bacterial Agents)
      0 (Oxazolidinones)
      ISQ9I6J12J (Linezolid)
    • Publication Date:
      Date Created: 20240905 Date Completed: 20240926 Latest Revision: 20241008
    • Publication Date:
      20241008
    • Accession Number:
      10.1021/acs.jmedchem.3c02061
    • Accession Number:
      39236219