2,3-Dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents: Design, synthesis, biological evaluation and SAR studies

• DOI: 10.1016/j.ejmech.2011.03.002
• Publication Date: 2011-03-09T15:26:01Z
• Authors: Mohammad Saquib; Irfan Husain; Smriti Sharma; Garima Yadav; Vipul K. Singh; Sandeep K. Sharma; Priyanka Shah; Mohammad Imran Si...; Brijesh Kumar; Jawahar Lal; Girish K. Jain; Brahm S. Srivastava; Ranjana Srivastava; Arun K. Shaw
• Keywords: Dose-Response Relationship, Drug; Molecular Structure; Cell Survival; Antitubercular Agents; Stereoisomerism; Microbial Sensitivity Tests; Mycobacterium tuberculosis; 01 natural sciences; Cell Line; 0104 chemical sciences; 3. Good health; Mice; Structure-Activity Relationship; Pyrones; Drug Design; Chlorocebus aethiops; Animals; Vero Cells

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.