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It is activated by the enzyme Deazaflavin-dependent nitroreductase (Ddn) present in<jats:italic>Mycobacterium tuberculosis<\/jats:italic>which catalyzes the reduction of PA-824, resulting in the release of lethal reactive nitrogen species (RNS) within the bacteria. In this context, PA-824 was analyzed for its activity against latent tuberculosis under anaerobic conditions and compared with rifampicin (RIF) and pyrazinamide (PZA). Recent mutagenesis studies have identified A76E mutation which affects the above mentioned catalysis and leads to PA-824 resistance. Hence, novel analogues which could cope up with their binding to mutant Ddn receptor were also identified through this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PA-824 at an optimum concentration of 12.5\u00a0\u03bcg\/ml showed enhanced bactericidal activity, resulting in 0\u00a0CFU\/ml growth when compared to RIF and PZA at normal pH and anaerobic condition. Further docking studies revealed that a combinatorial structure of PA-824 conjugated with moxifloxacin (ligand 8) has the highest binding affinity with the wild type and mutant Ddn receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PA-824 has been demonstrated to have better activity under anaerobic condition at 12.5\u00a0\u03bcg\/ml, indicating an optimized dose that is required for overcoming the detoxifying mechanisms of<jats:italic>M<\/jats:italic>.<jats:italic>tuberculosis<\/jats:italic>and inducing its death. 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