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Home / Publicações / Inhibition of drug efflux in mycobacteria with phenothiazines and other putative efflux inhibitors.

Inhibition of drug efflux in mycobacteria with phenothiazines and other putative efflux inhibitors.

  • Autores: Ainsa JA, Amaral L, Rodrigues L, Viveiros M
  • Journal: Recent Patents on Anti-Infective Drug Discovery
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Inhibition+of+drug+efflux+in+mycobacteria+with+phenothiazines+and+other+putative+efflux+inhibitors

Mycobacteria are responsible for some of the oldest diseases known to man, usually associated with high morbility and mortality rates. An example is tuberculosis (TB), a major public health problem that accounts for eight million new cases each year. Furthermore, the increase of multidrug and extremely-drug resistance seriously threatens the success of the TB control programmes. Resistance to anti-mycobacterial drugs is often due to spontaneous mutations in target genes, followed by selection of resistant mutants during treatment. However, this does not explain all cases of drug resistance and other mechanism(s) may be involved, namely efflux pumps that extrude the drug to the exterior of the cell. Efflux pumps are becoming attractive drug targets for the development of new anti-mycobacterial compounds and several efflux inhibitors have been developed and published in patent applications (i.e., WO2004062674, US2004204378, US2003118541, WO2008141012, WO2009110002, WO2010054102). However, none of these inhibitors is used in clinical practice. This review will focus on the potential use of efflux inhibitors as adjuvants of the anti-mycobacterial therapy, an approach that may restore the activity of antibiotics that are subject to efflux and render the mycobacteria more susceptible to drugs transported by these pumps.

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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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