Discovery of antipsychotic loxapine derivatives against intracellular multidrug-resistant bacteria

  • RSC Med Chem. 2022 Aug 11;13(11):1361-1366. doi: 10.1039/d2md00182a.
Hsueh-Chun Lin  1 ,  Yi-Lun Wu  2 ,  Cheng-Yun Hsu  1 ,  Man-Yi Lin  2 ,  Ling-Han Chen  1 ,  Chung-Wai Shiau  2 ,  Hao-Chieh Chiu  1  3
Affiliations
  • 1. Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University Taipei 10048 Taiwan [email protected].
  • 2. Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University Taipei 11221 Taiwan [email protected].
  • 3. Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University Taipei 10021 Taiwan.
PMID: 36439974 DOI: 10.1039/d2md00182a
Abstract

The emergence and spread of multidrug-resistant bacteria highlight the need for new Antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in macrophages and epithelial cells. Moreover, intra-macrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes and methicillin-resistant Staphylococcus aureus are also susceptible to SW14. Overall, our findings suggest that SW14 has a broad-spectrum activity against intracellular bacteria.