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Synthesis of PA-824
M. A. Marsini, P. J. Reider*, E. J. Sorensen*
Princeton University, USA
21 December 2010 (online)
PA-824 is in phase II clinical trials for the treatment of tuberculosis. It inhibits cell wall formation by disrupting mycolic acid synthesis in Mycobacterium tuberculosis. The mechanism of action entails reduction of the nitroimidazole ring by Fgd1, an F420-dependent glucose-6-phosphate dehydrogenase, and Rv3547, a deazaflavin-dependent nitroreductase, to afford the des-nitro compound and nitric oxide.