An alkylaminoquinazoline restores antibiotic activity in Gram-negative resistant isolates
Mahamoud, Abdallah and Chevalier, Jacqueline and Baitiche, Milad and Adam, Elissavet and Pagès, Jean-Marie,, 157, 566-571 (2011),
doi = https://doi.org/10.1099/mic.0.045716-0,
publicationName = Microbiology Society,
issn = 1350-0872,
abstract= To date, various bacterial drug efflux pump inhibitors (EPIs) have been described. They exhibit variability in their activity spectrum with respect to antibiotic structural class and bacterial species. Among the various 4-alkylaminoquinazoline derivatives synthesized and studied in this work, one molecule, 1167, increased the susceptibility of important human-pathogenic, resistant, Gram-negative bacteria towards different antibiotic classes. This 4-(3-morpholinopropylamino)-quinazoline induced an increase in the activity of chloramphenicol, nalidixic acid, norfloxacin and sparfloxacin, which are substrates of the AcrAB-TolC and MexAB-OprM efflux pumps that act in these multidrug-resistant isolates. In addition, 1167 increased the intracellular concentration of chloramphenicol in efflux pump-overproducing strains. The rate of restoration depended on the structure of the antibiotic, suggesting that different sites in the efflux pumps may be involved. A molecule exhibiting a morpholine functional group and a propyl extension of the side chain was more active.,
language=,
type=