Design, synthesis and biological evaluation of indole and N-benzylated indole Mannich bases as potent antitubercular agents

Abstract

Though effective medicines have been available for treating drug-susceptible tuberculosis infections, the chances go from bleak to null as we move from multidrug resistant (MDR) to extremely drug resistant (XDR) or totally drug resistant (TDR) disease. Coordinated efforts made by international community have resulted in the identification of a few important anti TB agents like BM212, SQ109, AZD5847 and Sutezolid which are in the late phases of clinical trials. After Rifampicin, only two drugs Bedaquiline (2013) and Delaminid (2014) have been approved for the treatment of tuberculosis. This clearly shows the need for new leads towards fighting tuberculosis. In our present work, we have synthesized a series of indole and substituted indole Mannich bases designed by using structural features of BM212. Further, these synthesized derivatives have been analyzed by IR, NMR and mass spectral studies and are screened for anti-tubercular and antimicrobial activity. Among these, 23 compounds have shown potent anti TB activity with a MIC ≤3.12 µg/mL against M. tuberculosis
H37Rv. We report here the synthesis, screening data and SAR studies of indole and substituted indole derivatives as antitubercular agents.