The mechanism of action of 5-nitrothiophenes against Mycobacterium tuberculosis

On using the streptomycin-starved 18b strain as a model for non-replicating Mycobacterium tuberculosis, a 5-nitrothiophene compound was identified as being highly active but not cytotoxic. Mutants resistant to 5-nitrothiophenes were found be cross-resistant to the nitroimidazole PA-824, and unable to produce the F420 co-factor. Furthermore, 5-nitrothiophenes were shown to be activated by the F420-dependent nitroreductase, Ddn, and to release nitric oxide, a mechanism of action identical to that described for nitroimidazoles.