To discover new compounds for combating drug-resistant tuberculosis, Pethe et al. conducted a high-content phenotypic screen against macrophages infected with Mycobacterium tuberculosis. This identified a class of imidazopyridine amide compounds that targeted the respiratory cytochrome bc1 complex of M. tuberculosis to inhibit growth. Optimization of one compound resulted in Q203, which potently inhibited the growth of multi- and extensively-drug-resistant clinical isolates of M. tuberculosis; the compound alsoreduced bacterial load and improved lung pathology in a mouse model. The authors suggest that Q203 could be a new clinical candidate against tuberculosis.
References
Pethe, K. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nature Med. 19, 1157–1160 (2013)
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Harrison, C. A new lead against drug-resistant tuberculosis. Nat Rev Drug Discov 12, 742 (2013). https://doi.org/10.1038/nrd4142
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DOI: https://doi.org/10.1038/nrd4142