2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents: design, synthesis, biological evaluation and SAR studies.
Saquib M, Husain I, Sharma S, Yadav G, Singh VK, Sharma SK, Shah P, Siddiqi MI, Kumar B, Lal J, Jain GK, Srivastava BS, Srivastava R, Shaw AK.
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.