title: Antimycobacterial activities of oxazolidinones: a review.
abstract: Oxazolidinones are a new class of totally synthetic antibacterial agents with wide spectrum of activity against a variety of clinically significant susceptible and resistant bacteria. These compounds have been shown to inhibit translation at the initiation phase of protein synthesis. DuP-721, the first oxazolidinone showed good activity against M. tuberculosis when given orally or parenterally to experimental animals but was not developed further due to lethal toxicity in animal models. Later two oxazolidinones, PNU-100480 and Linezolid, demonstrated promising antimycobacterial activities in the murine model. While Linezolid has been approved for clinical use, PNU-100480 was not been developed further. DA-7867 showed good in vitro and better in vivo efficacy than Linezolid but was poorly tolerated in rat toxicology studies. The antimycobacterial activity of AZD-2563 has not been explored. RBx 7644 had modest antimycobacterial activity while RBx 8700 has potent antibacterial and concentration dependent activity against all slow growing mycobacteria. It demonstrated better activity than RBx 7644 against MDR strains of M. tuberculosis along with intracellular activity. Toxicity, especially myelosuppression, has been an important limiting factor for development of an oxazolidinones. The GM-CSF assay has helped in selecting molecules with less myleosuppressive potential. We report, a review on the promising antituberculosis activities of the class oxazolidinones.
authors.affiliation: Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No. 20, Sector -18, Udyog Vihar Industrial Area, Gurgaon-122 001, India. ruchi.sood@ranbaxy.com
authors.forename: R
authors.initials: R
authors.lastname: Sood
authors.forename: T
authors.initials: T
authors.lastname: Bhadauriya
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.forename: R
authors.initials: R
authors.lastname: Gautam
authors.forename: S
authors.initials: S
authors.lastname: Malhotra
authors.forename: T K
authors.initials: TK
authors.lastname: Barman
authors.forename: D J
authors.initials: DJ
authors.lastname: Upadhyay
authors.forename: A
authors.initials: A
authors.lastname: Rattan
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects*; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid