Winkelhake Connor M, Rimal Binayak, Thomas Ben A, Huisken Joe B, Lamichhane Gyanu, Ippoliti J Thomas
Department of Chemistry, University of St. Thomas, 2115 Summit Ave, St. Paul, MN 55105, United States.
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.
Bioorg Med Chem Lett. 2025 Dec 1;128:130359. doi: 10.1016/j.bmcl.2025.130359. Epub 2025 Aug 6.
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.
脓肿分枝杆菌感染是一个重大的治疗挑战，这是由于缺乏有效的治疗方法，以及目前针对该适应症推荐的强化多药治疗方案。恶唑烷酮类抗生素如利奈唑胺已被用于治疗这种复杂疾病。利用一种策略性的结构扩展策略，通过将肟、腈、酰胺、偕胺肟和肟酯官能团引入到先前报道的苯并二恶英骨架中，合成了五种新型恶唑烷酮衍生物。评估了这些衍生物对脓肿分枝杆菌的体外活性，其中偕胺肟衍生物表现出优于利奈唑胺的活性。
