Addressing the stability of C-capped dipeptide efflux pump inhibitors thatpotentiate the activity of levofloxacin in Pseudomonas aeruginosa

Synthetic optimization of a biologically labile class of dipeptides that fu nction as efflux pump inhibitors to potentiate the antibacterial agent levo floxacin in Pseudomonas aeruginosa has led to the discovery of a related se ries of compounds that are completely stable in a variety of biological mat rices. Other than the stability profile, the in vitro profile of the new se ries is essentially identical to that observed with the original one. A pro totypical compound from the new series demonstrates potentiation in an in v ivo model of infection. (C) 2001 Elsevier Science Ltd. All rights reserved.