Studies from our laboratory have indicated that amides derived from 3-amino-1,5-diphenylpentane can potentiate the antibiotic activity of clarithromycin against Escherichia coli. In the present study, the impact on activity of reversing the amide moiety within this series of compounds was investigated, and desoxy derivatives of three of the reversed amide derivatives were also synthesized and evaluated. In general, the reversed amides exhibited enhanced potency as potentiators of antibiotic activity against E. coli. Compound 7 (the N1-1,2,5-triaminopentyl amide of 3,3-dibenzylpropanoic acid) proved to be the most active analog, lowering the MIC of clarithromycin by 512-fold and having 128-fold greater potency than PAβN. The desoxy derivatives 22 and 23 were 8-fold and 4-fold more potent than their carboxamides (4 and 11) respectively. Compounds 7 and 22 were effective at potentiating the activity of not only clarithromycin, but also of other antibiotics, including minocycline, novobiocin, clindamycin, and azithromycin. The collective results of cell-based studies suggest that the antibiotic potentiating activities of 7 and 22 reflect contributions from both membrane permeabilization and efflux pump inhibition, but not from disruption of the proton gradient or potential across the membrane.