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Review

Discovery and Development of Highly Potent Inhibitors of Mycobacterium tuberculosis Growth In Vitro

E. Lucile White  1 , Clinton Maddox  1 , Ntsang Miranda Nebane  1 , Nichole A. Tower  1 , Sara McKellip  1 , Anna Manuvakhova  1 , Lakshmi Reddy  1 , Melinda Sosa  1 , Lynn Rasmussen  1 , Kanupriya Whig  1 , Subramaniam Ananthan  1 , Shichun Lun  2 , William Bishai  2 , Warren S. Weiner  3 , Frank Schoenen  3 , Apurba Dutta  3 , Jeffrey Aubé  3   4
In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010.
[updated ].
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Review

Discovery and Development of Highly Potent Inhibitors of Mycobacterium tuberculosis Growth In Vitro

E. Lucile White et al.
Free Books & Documents

Excerpt

Tuberculosis (TB) represents one of the top public health concerns worldwide. Over 2 billion people are infected with Mycobacterium tuberculosis (M. tb), the etiological agent of TB, resulting in 9.4 million new cases of active TB and 1.7 million deaths in 2009. The 1970s multidrug regimen for treating TB, recommended today by the WHO, has not been sufficient to eliminate TB in part due to the appearance of HIV/AIDS, failure of treatment programs, and enhanced transmission in hospitals and prisons. The recommended combination therapy for TB is lengthy and cumbersome since it can require medication of up to four drugs daily for 6–12 months. Limited healthcare system resources often lead to treatment interruption or failure, exacerbating drug resistance problems in places least capable of combating this disease. Thus, the discovery of new types of anti-tubercular drugs acting on novel drug targets with no cross-resistance to any existing drugs is urgently needed. Screening of ~330,000 compounds from the NIH Small Molecule Repository for their ability to inhibit the growth of M. tb identified a number of novel scaffolds with anti-tubercular activity. In this report, we discuss the development of one of those scaffolds leading to the probe ML242 (CID 2792221).

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