Discovery of new dibenzodiazepine derivatives as antibacterials against intracellular bacteria

The emergence and spread of multidrug-resistant bacteria underscore the critical need for novel antibacterial interventions. In our screening of 12 synthesized thienobenzodiazepines, pyridobenzodiazepines, and dibenzodiazepines, we successfully identified a small molecule compound SW33. Notably, SW33 demonstrated potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in both macrophages and epithelial cells. Furthermore, SW33 was also effective against intramacrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes. These significant findings suggest that SW33 possesses broad-spectrum activity against intracellular bacteria. A tricyclic core derivative, SW33, showed potency against intracellular drug-resistant strains of S. typhimurium and other intracellular pathogens with no toxicity, indicating a broad-spectrum activity against intracellular bacteria.