Design, Synthesis, and Structure–Activity Correlations of Novel Dibenzo[<i>b</i>,<i>d</i>]furan, Dibenzo[<i>b</i>,<i>d</i>]thiophene, and <i>N</i>-Methylcarbazole Clubbed 1,2,3-Triazoles as Potent Inhibitors of <i>Mycobacterium tuberculosis</i>

A molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. In this study, 1,2,3-triazole-based <i>Mycobacterium tuberculosis</i> inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo­[<i>b</i>,<i>d</i>]­furan, and dibenzo­[<i>b</i>,<i>d</i>]­thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. Structure–activity correlations and in vitro activity against <i>M. tuberculosis</i> strain H37Rv of new analogues revealed the order: dibenzo­[<i>b</i>,<i>d</i>]­thiophene > dibenzo­[<i>b</i>,<i>d</i>]­furan > 9-methyl-9<i>H</i>-carbazole series. Two of the most potent <i>M. tuberculosis</i> inhibitors <b>13h</b> and <b>13q</b> with MIC = 0.78 μg/mL (∼1.9 μM) displayed a low cytotoxicity and high selectivity index (50–255) against four different human cancer cell lines. These results together provided the potential importance of molecular hybridization and the development of triazole clubbed dibenzo­[<i>b</i>,<i>d</i>]­thiophene-based lead candidates to treat mycobacterial infections