title: Oxazolidinones as Anti-tubercular Agents: Discovery, Development and Future Perspectives.
abstract: TB drug development pipeline represents varied structural classes of molecules. Oxazolidinones represent synthetic anti-bacterial agents with unique mechanism of action having wide spectrum of activity, oral bioavailability and well established SAR. They act by inhibiting translation at the initiation phase of protein synthesis. Linezolid was the first oxazolidinone to reach the market in the year 2000 for the treatment of methicillin-resistant staphylococcal and vancomycin-resistant enterococcal infections. Oxazolidinones have shown very good anti-mycobacterial activities. Several oxazolidinones are currently in development for their possible use in TB therapy. Oxazolidinones are classified on the basis of C-ring modifications. DuP-721 was the first oxazolidinone having good anti-TB activity. Linezolid, sutezolid and AZD5847 are in clinical development. Several other C-ring modifications have shown promising results. The usefulness of these oxazolidinones in the drug resistant TB is already established. Toxicity, especially myelosuppression, has been an important limiting factor for their development.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Jadhavar
authors.forename: Maulikkumar D
authors.initials: MD
authors.lastname: Vaja
authors.forename: Tejas M
authors.initials: TM
authors.lastname: Dhameliya
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India. akchakraborti@niper.ac.in.
authors.forename: Asit K
authors.initials: AK
authors.lastname: Chakraborti
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D023303:Oxazolidinones