Design, Synthesis and Biological Evaluation of New Substituted Sulfonamide Tetrazole Derivatives as Antitubercular Agents

摘要

The 1,2,4 triazole and tetrazole pharmacophore is still considered a viable lead structure for the synthesis of more efficacious and broad spectrum anti-microbial agents. In this communication, a new class of highly potent anti-tuberculosis agents are reported. Designed and synthesized a series of 18 compounds and evaluated them for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Among the compounds tested, five compounds exhibited moderate anti- TB activity (MIC = 6.25 μg/mL); compounds 8a, 8d, 8i, 9b and 9f displayed good activity (Minimal inhibition concentration (MIC) = 3.12 μg/mL), while compounds 8e, 8g, 8h, 9d and 9h exhibited excellent activity (MIC = 1.56 mg/mL) against the growth of Mycobacterium tuberculosis H37Rv. Furthermore, they displayed no toxicity against CHO-K1 cell lines at a concentration of 100 mM. These investigated analogues have emerged as potential leads to extend the scope of the anti-tubercular research. Additionally, the most active compounds were docked to enzyme MTB CytP51 (2CIB.pdb) to understand ligand-receptor binding interactions.