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

Abstract

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 H37Rv (ATCC 27294) resulted two compounds 4x and 4z (MIC: 6.25 μg/mL) as most promising antitubercular agents with low cytotoxicity.