Quinazoline derivatives are efficient chemosensitizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa resistant strains

Jacqueline Chevalier , Abdallah Mahamoud , Milad Baitiche , Elissavet Adam , Miguel Viveiros , Adriana Smarandache (1) , Andra Militaru (1) , Mihail L. Pascu (1) , Leonard Amaral , Jean-Marie Pagès

1 INFLPR - National Institute for Laser, Plasma and Radiation Physics

Among the three series of quinazoline derivatives synthesised and studied in this work, some molecules increase the antibiotic susceptibility of Gram-negative bacteria presenting multidrug-resistant phenotypes. -alkyl compounds induced an increase in the activity of chloramphenicol, nalidixic acid and sparfloxacin, which are substrates of the AcrAB-TolC and MexAB-OprM efflux pumps in clinical isolates. These molecules are able to increase the intracellular concentration of chloramphenicol in efflux pump-overproducing strains. Their activity depends on the antibiotic structure, suggesting that different sites may be involved for the recognition of substrates by a given efflux pump. Quinazoline molecules exhibiting a nitro functional group are more active, and structure-activity relationship studies may be undertaken to identify the pharmacophoric group involved in the AcrB and MexB affinity sites.

Mots clés: Efflux pump inhibitor; Enterobacter aerogenes; Klebsiella pneumoniae; Pseudomonas aeruginosa; Antibiotic resistance; Quinazoline derivatives; Efflux pumps

Jacqueline Chevalier, Abdallah Mahamoud, Milad Baitiche, Elissavet Adam, Miguel Viveiros, et al.. Quinazoline derivatives are efficient chemosensitizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa resistant strains. International Journal of Antimicrobial Agents, 2010, 36 (2), pp.164. ⟨10.1016/j.ijantimicag.2010.03.027⟩. ⟨hal-00601191⟩