Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis.

@article{Hong2017RationalDS,
  title={Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis.},
  author={W. David Hong and Peter D Gibbons and Suet C. Leung and Richard K. Amewu and Paul A. Stocks and Andrew V. Stachulski and Pedro Horta and Maria Lurdes S Cristiano and Alison E. Shone and Darren Michael Moss and Alison Ardrey and Raman M Sharma and Ashley J. Warman and Paul T P Bedingfield and Nicholas E. Fisher and Ghaith Aljayyoussi and Sally Mead and Maxine Caws and Neil G Berry and Stephen A Ward and Giancarlo A Biagini and Paul M O'neill and Gemma L Nixon},
  journal={Journal of medicinal chemistry},
  year={2017},
  volume={60 9},
  pages={3703-3726}
}
A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified ∼100 hits and four distinct chemotypes, the most promising of which contained… CONTINUE READING