Almost all antibiotics target the same cellular mechanisms: cell wall synthesis, nucleic acid synthesis, or protein synthesis, and many bacterial pathogens have become adept at evading these mechanisms. Because of the success of the anti-tubercular drug Bedaquiline, ATP synthase, which is a protein essential for all life, has been explored as a new target for antibiotic development. Recently our laboratory developed quinoline derived <i>Pseudomonas aeruginosa</i> ATP synthase inhibitors; however, there were issues with accumulation, which resulted in only weak antibiotic activity. To overcome this issue, a series of quinoline analogs have been synthesized with increased lipophilicity to promote diffusion of the compounds through the PA poly-anionic outer membrane.

Synthesis of gram-negative ATP synthase inhibitors

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