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Overview
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Background
PA-824, a bicyclic nitroimidazoles, is an anti-tuberculosis (TB) agent that exerts potent in vitro activity against Mycobacterium tuberculosis with the minimal inhibition concentration (MIC) ranging from 0.015 μg/ml to 0.25 μg/ml and remains actively against a wide range of isolates that are resistant to commonly used anti-TB agents leading to its successful application in the treatment of TB [1].
PA-824 has been found to exhibit bactericidal activity against replicating bacilli and non-replicating bacilli under hypoxic or prolonged culture conditions in a dose dependent fashion through two possible mechanisms, which include PA-824 induced inhibition of ketomycolate synthesis and PA-824 mediated donation of nitric oxide during enzymatic nitro-reduction [1].[1] Ahmad Z, Peloquin CA, Singh RP, Derendorf H, Tyagi S, Ginsberg A, Grosset JH, Nuermberger EL. PA-824 exhibits time-dependent activity in a murine model of tuberculosis. Antimicrob Agents Chemother. 2011 Jan;55(1):239-45. doi: 10.1128/AAC.00849-10. Epub 2010 Oct 11.
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