Bedquiline (BDQ), a novel newly developed antibiotic, significantly inhibits the F0 c-ring of F-ATP synthase (F-ATPase) in drug resistant M. tuberculosis by stopping rotation and ATP production, thereby facilitating apoptosis. However, due to differences in amino acid coding, binding affinities of other bacteria are highly reduced. Primarily focusing on Gram-negative E. coli, analogs of BDQ were synthesized to determine the efficacy of distinct functional groups to create the most potent analog. Strong differences in hydrophobic, steric, and polar amino acids affecting binding of the c-ring at positions 35, 65, 67-69, and 72. Synthesized analogs’ potency will be determined via inside-out vesicle H+ pumping and bacterial assays.
