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

• Autores: Adam E, Amaral L, Baitiche M, Chevalier J, Mahamoud A, Militaru A, Pagès JM, Pascu ML, Smarandache A, Viveiros M
• Journal: International Journal of Antimicrobial Agents
• Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Quinazoline+derivatives+are+efficient+chemosensitizers+of+antibiotic+activity+in+Enterobacter+aerogenes%2C+Klebsiella+pneumoniae+and+Pseudomonas+aeruginosa+resistant+strains

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.