Synthesis and antibacterial activity of novel benzodioxin-containing oxazolidinones against M. abscessus

  • Bioorg Med Chem Lett. 2025 Dec 1:128:130359. doi: 10.1016/j.bmcl.2025.130359.
Connor M Winkelhake  1 ,  Binayak Rimal  2 ,  Ben A Thomas  1 ,  Joe B Huisken  1 ,  Gyanu Lamichhane  3 ,  J Thomas Ippoliti  4
Affiliations
  • 1. Department of Chemistry, University of St. Thomas, 2115 Summit Ave, St. Paul, MN 55105, United States.
  • 2. Taskforce for Resistance Emergence & Antimicrobial Technology and Center for Non-tuberculous Mycobacteria and Bronchiectasis, Department of Medicine, Johns Hopkins University, 1550 Orleans St, Baltimore, MD 21287, United States.
  • 3. Taskforce for Resistance Emergence & Antimicrobial Technology and Center for Non-tuberculous Mycobacteria and Bronchiectasis, Department of Medicine, Johns Hopkins University, 1550 Orleans St, Baltimore, MD 21287, United States. Electronic address: [email protected].
  • 4. Department of Chemistry, University of St. Thomas, 2115 Summit Ave, St. Paul, MN 55105, United States. Electronic address: [email protected].
PMID: 40780460 DOI: 10.1016/j.bmcl.2025.130359
Abstract

Mycobacterium abscessus infections represent a significant treatment challenge, owing to the lack of effective therapies, and the intensive multidrug regimens currently recommended for this indication. Oxazolidinone antibiotics such as linezolid have been used to treat this complex disease. Utilizing a strategic structural extension strategy, five novel Oxazolidinone derivatives were synthesized by the introduction of oxime, nitrile, amide, amidoxime, and oxime ester functional groups to a previously reported benzodioxin-scaffold. The in vitro activities of these derivatives against M. abscessus were assessed, with the amidoxime derivative exhibiting activity superior to linezolid.

Keywords
Antibacterial activities; Antibiotics; Mycobacterium abscessus; Mycobacteroides abscessus; Oxazolidinones; Synthesis.
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