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- W2893063815 abstract "Abstract The quinolone decoquinate is coadministered with feed for treatment of parasites which cause coccidiosis in poultry. However, from a drug-development perspective, the biological activity is often not adequately exploited due to poor physicochemical properties. Here we convert decoquinate into N -alkyl quinolone amides that, in contrast to decoquinate, are active against the tuberculosis bacterium with MIC 90 values ranging from 1.4 to 3.64 µM, and quinoline O -carbamates active against apicomplexan parasites that cause malaria, toxoplasmosis, and neosporosis with IC 50 values of 0.32–1.5 nM for the best derivative. Uniquely for the TB-active amides, disruption of cell wall homoeostasis is identified as one target. With IC 50 values against fetal lung fibroblast cells of 40 to >100 μM, the derivatives are selective for the pathogens. Structures of the most active derivatives are determined by NMR spectroscopy and X-ray crystallography. Analogues lacking the decyl side chain of decoquinate are inactive." @default.
- W2893063815 created "2018-10-05" @default.
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- W2893063815 date "2018-10-02" @default.
- W2893063815 modified "2023-10-10" @default.
- W2893063815 title "Accessible and distinct decoquinate derivatives active against Mycobacterium tuberculosis and apicomplexan parasites" @default.
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- W2893063815 doi "https://doi.org/10.1038/s42004-018-0062-7" @default.
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