Discovery of antipsychotic loxapine derivatives against intracellular multidrug-resistant bacteria

Area of Science:

• Microbiology
• Medicinal Chemistry
• Infectious Diseases

Background:

• The rise of multidrug-resistant bacteria necessitates novel therapeutic approaches.
• Intracellular bacterial infections pose significant treatment challenges.

Purpose of the Study:

• To identify novel small molecules with potent antibacterial activity against intracellular pathogens.
• To evaluate the efficacy of newly synthesized dibenzoxepines against resistant bacterial strains.

Main Methods:

• Screening of 24 novel dibenzoxepines for antibacterial activity.
• Testing compound SW14 against intracellular multidrug-resistant *Salmonella typhimurium* in macrophages and epithelial cells.
• Assessing SW14's activity against other intracellular bacteria, including *Salmonella typhi*, *Yersinia enterocolitica*, *Listeria monocytogenes*, and methicillin-resistant *Staphylococcus aureus*.

Main Results:

• Compound SW14 demonstrated potent inhibition of intracellular multidrug-resistant and fluoroquinolone-resistant *S. typhimurium*.
• SW14 was effective against intracellular *S. typhi*, *Y. enterocolitica*, *L. monocytogenes*, and MRSA.
• The compound exhibited broad-spectrum activity against a range of intracellular bacterial pathogens.

Conclusions:

• SW14 is a promising lead compound for developing new antibacterial agents targeting intracellular bacteria.
• The findings support the potential of dibenzoxepines as a novel class of antibacterials.
• SW14 warrants further investigation for its therapeutic potential against resistant intracellular infections.