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

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.

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About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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