title: Quinazoline derivatives are efficient chemosensitizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa resistant strains.
abstract: Amongst 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. N-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.
authors.affiliation: UMR-MD1, Facultés de Médecine et de Pharmacie, Université de la Méditerranée, IFR88, Marseille, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Abdallah
authors.initials: A
authors.lastname: Mahamoud
authors.forename: Milad
authors.initials: M
authors.lastname: Baitiche
authors.forename: Elissavet
authors.initials: E
authors.lastname: Adam
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Adriana
authors.initials: A
authors.lastname: Smarandache
authors.forename: Andra
authors.initials: A
authors.lastname: Militaru
authors.forename: Mihail L
authors.initials: ML
authors.lastname: Pascu
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D021902:Enterobacter aerogenes / Q000187:drug effects*; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011799:Quinazolines; D009268:Nalidixic Acid; D002701:Chloramphenicol; C061363:sparfloxacin