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Home / Publicações / Natural isoflavone biochanin A as a template for the design of new and potent 3-phenylquinolone efflux inhibitors against Mycobacterium avium

Natural isoflavone biochanin A as a template for the design of new and potent 3-phenylquinolone efflux inhibitors against Mycobacterium avium

  • Autores: Barreca ML, Cannalire R, Cecchetti V, Couto I, Felicetti T, Machado D, Manfroni G, Massari S, Sabatini S, Santos Costa S, Tabarrini O, Viveiros M
  • Ano de Publicação: 2017
  • Journal: European Journal of Medicinal Chemistry
  • Link: https://www.ncbi.nlm.nih.gov/pubmed/28964936

Mycobacterium avium is a difficult-to-treat pathogen able to quickly develop drug resistance. Like for other microbial species, overexpression of efflux pumps is one of the main mechanisms in developing multidrug resistance. Although the use of efflux pumps inhibitors (EPIs) represents a promising strategy to reverse resistance, to date few M. avium EPIs are known. Recently, the authors showed that in-house 2-phenylquinoline S. aureus NorA EPIs exhibited also a good activity against M. avium efflux pumps. Herein, they report a series of 3-phenylquinolones designed by modifying the isoflavone biochanin A, a natural EPI of the related M. smegmatis. They have taking into account some important SAR information obtained around the 2-phenylquinoline NorA EPIs. The 3-phenylquinolones inhibited M. avium efflux pumps with derivatives 1e and 1g that displayed the highest synergistic activity against all the strains considered in the study, bringing down (from 4- to 128-fold reduction) the MIC values of macrolides and fluoroquinolones.

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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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