IITR08367 is a potent inhibitor of the efflux pump Acinetobacter baumannii Fosfomycin Efflux pump (AbaF), designed to enhance the antibacterial activity of Fosfomycin against Acinetobacter baumannii. It operates by disrupting the Fosfomycin/H+ antiport activity.

IITR08367 enhances the activity of Fosfomycin against AbaF-expressing Escherichia coli strains in a concentration-dependent manner (0-50 μM), extending the post-antibiotic effect of Fosfomycin by 30 minutes at 50 μM. At 25 μM for 16 minutes, IITR08367 disrupts the H+ gradient across the membrane and ultimately inhibits the efflux pump driven by this gradient without causing membrane damage. When used in combination at 100 μM for 12 hours with Fosfomycin (64 mg/L), it inhibits the growth of A. baumannii RPTC-15. IITR08367 at 100 μM can eliminate the biofilm-forming ability of A. baumannii, with or without the presence of Fosfomycin. In the concentration range of 12.5-200 μM, IITR08367 exhibits no toxicity to red blood cells.

The combined administration of IITR08367 (i.p.; 30 mg/kg; every 12 hours for 54 hours) and Fosfomycin significantly improved the condition of mice with urinary tract infections caused by A. baumannii RPTC-15, resulting in tissue ultrastructure similar to that of uninfected mice.