Journal
MEDICINAL CHEMISTRY
Volume 5, Issue 2, Pages 197-207Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/157340609787582882
Keywords
New drug target for Mycobacterium tuberculosis; menaquinone biosynthesis; MenA; MenA inhibitors; nonreplicating Mycobacterium tuberculosis
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Funding
- Institute of Health and Colorado State University for generous
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Potent inhibitors of MenA (1,4-dihydroxy-2-naphtoate prenyltrasferase) in Mycobacterium tuberculosis are identified, and are also effective in inhibiting growth of Mycobacterium tuberculosis at low concentrations. The MenA inhibitors possess common chemical structural features of (alkylamino)oalkoxyphenyl)(phenyl) methanones. Significantly, the MenA inhibitors can be synthesized in a few steps with high overall yields. The representative MenA inhibitors are highly effective in killing nonreplicating Mycobacterium tuberculosis that is evaluated by using the Wayne low oxygen model. In addition, a series of drug resistant Mycobacterium spp. are sensitive to the MenA inhibitors. The results are expected to be of significance in terms of discovering new lead compounds that can be developed into new drugs to combat unmet diseases caused by Mycobacterium tuberculosis.
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