Antibacterial agent 128

Antibacterial agent 128 (compound 2d), bearing an hydroxypyridinone moiety with a cleavable linker, active on a large panel of strains of P. aeruginosa (MIC = 0.25-64 μg/mL), B. pseudomallei (MIC = 1-32 μg/mL) and B. thailandensis (MIC = 4-128 μg/mL). Moreover, Antibacterial agent 128 is active on the P. aeruginosa Ciprofloxacin-resistant strain AM85 without cytotoxicity^[1].
Using iron transport systems is a promising strategy to bypass the bacteria cell membrane and restore the activity of conventional antibiotics such as Ciprofloxacin. The siderophore analogs correspond to a mono-catechol or a hydroxypyridinone moiety recognized by both Pseudomonas and Burkholderia species. Physico-chemical studies show that (i) conjugates were unable to interact or cross the membrane by passive diffusion and (ii) conjugates with cleavable linker are stable in physiologic environment^[1].

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