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MenA Is a Promising Drug Target for Developing Novel Lead Molecules to Combat Mycobacterium tuberculosis

[ Vol. 5 , Issue. 2 ]

Author(s):

Michio Kurosu and Dean C. Crick   Pages 197 - 207 ( 11 )

Abstract:


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.

Keywords:

New drug target for Mycobacterium tuberculosis, menaquinone biosynthesis, MenA, MenA inhibitors, nonreplicating Mycobacterium tuberculosis

Affiliation:

Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523-1682, USA.



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