title: Nitroimidazoles for the treatment of TB: past, present and future.
abstract: Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed.
authors: Tuberculosis Research Section, LCID, NIAID, NIH, Room 2W20G, Building 33, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors: Tathagata
authors: T
authors: Mukherjee
authors: Helena
authors: H
authors: Boshoff
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D009593:Nitroimidazoles