title: Mechanism of action of 5-nitrothiophenes against Mycobacterium tuberculosis.
abstract: On using the streptomycin-starved 18b strain as a model for nonreplicating Mycobacterium tuberculosis, we identified a 5-nitrothiophene compound as 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 cofactor. 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.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Lausanne, Switzerland.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Hartkoorn
authors.forename: Olga B
authors.initials: OB
authors.lastname: Ryabova
authors.forename: Laurent R
authors.initials: LR
authors.lastname: Chiarelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Riccardi
authors.forename: Vadim
authors.initials: V
authors.lastname: Makarov
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D009593:Nitroimidazoles / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D009593:Nitroimidazoles; D013876:Thiophenes