Rational design, synthesis and evaluation of novel-substituted 1,2,3-triazolylmethyl carbazoles as potent inhibitors of Mycobacterium tuberculosis

Herein, we describe synthesis and antitubercular evaluation of novel-substituted 1,2,3-triazolylmethyl carbazoles rationally designed by incorporating two pharmacophoric heterocycles, viz. carbazole and triazole in one molecular frame. The new compounds 4a-z and 4aa-ac were obtained in very good yields using copper-catalysed Huisgen [3 + 2] cycloaddition reaction of 9-propynyl-9H-carbazole (2) with various aryl/alkyl azides 3a-z and 3aa-ac. Evaluation of all 29 new analogues for in vitro antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv (ATCC 27294) resulted two compounds 4x and 4z (MIC: 6.25 mu g/mL) as most promising antitubercular agents with low cytotoxicity.