Among Gram-negative bacteria, P. aeruginosa is often involved in nosocomial infections (6.2% of infected hospitalized patients) and belongs to first list of antibiotic-resistant “priority pathogens” reported by the World Health Organization. This bacterium is targeted due to its high level of resistance to antibiotics via a lack of membrane permeability or efflux. To overcome these phenomena, the use of iron transport systems is a promising Trojan Horse strategy to restore the activity of conventional antibiotics against this species. Iron is an essential micronutrient for the survival of bacteria, involved in many biological processes such as respiration, DNA synthesis… However, due to its low solubility in water, ferric iron has a low bioavailability. In conditions of limited iron access, many bacteria synthesize siderophores, molecules of low molecular weight, able to chelate the surrounding iron. Depending on their species, bacteria express several different types of TonB-dependent outer membrane receptors that recognize their endogenous siderophores but also xenosiderophores or synthetic siderophore-like compounds. These specific systems may allow the introduction of antibacterial agents by forming siderophore analog-antibiotic conjugates. Proof of concept has already been established with cefiderocol, a broad-spectrum antimicrobial catecholate-cephalosporin conjugate used for the treatment of infections in adult patients with limited treatment options such as multi-drug resistant strains of P. aeruginosa. Herein, we will describe the synthesis, the study and the antipseudomonal activities of new ciprofloxacin conjugates that may be internalized into bacteria via catecholate-type moieties.

Synthesis and study new iron chelator-ciprofloxacin conjugates: A Trojan Horse strategy against P. aeruginosa

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.