title: 2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents: design, synthesis, biological evaluation and SAR studies.
abstract: The alarming resurgence of tuberculosis (TB) underlines the urgent need for development of new and potent anti-TB drugs. Towards this goal we herein report the design and synthesis of 2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents. These easily accessible, small molecules were found to exhibit in vitro activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.78 μg/mL to 25 μg/mL. A detailed SAR study on these hex-2-enopyranosid-4-uloses led to the identification of compound 5g (S007-724) which on the basis of low MIC (0.78 μg/mL-M. tuberculosis H37Rv; 1.56 μg/mL-MDR, SDR strains of M. tuberculosis; 0.78 μg/mL-inhibition of intracellular replication of M. tuberculosis) and SI value of 13.5 has been identified as a promising lead molecule.
authors: Medicinal and Process Chemistry Division, Central Drug Research Institute (CDRI), CSIR, Lucknow 226001, India.
authors: Mohammad
authors: M
authors: Saquib
authors: Irfan
authors: I
authors: Husain
authors: Smriti
authors: S
authors: Sharma
authors: Garima
authors: G
authors: Yadav
authors: Vipul K
authors: VK
authors: Singh
authors: Sandeep K
authors: SK
authors: Sharma
authors: Priyanka
authors: P
authors: Shah
authors: Mohammad Imran
authors: MI
authors: Siddiqi
authors: Brijesh
authors: B
authors: Kumar
authors: Jawahar
authors: J
authors: Lal
authors: Girish K
authors: GK
authors: Jain
authors: Brahm S
authors: BS
authors: Srivastava
authors: Ranjana
authors: R
authors: Srivastava
authors: Arun K
authors: AK
authors: Shaw
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D011753:Pyrones; C560933:S007 724