Synthesis and Biological Evaluation of N-Benzylindolylchalcone Analogs as Antitubercular Agents

Abstract

A new series of N-benzylindolylchalcone analogs has been designed, synthesized, and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The synthesis of N-benzylatedindole-3-carbaldehyde derivatives, namely, -1-(2-methylbenzyl)-1H-indole-3-carbaldehyde (S2I1)1-(3-methylbenzyl)-1Hindole-3-carbaldehyde (S2I2), was achieved by N-benzylation of indole-3-carbaldehyde using a mixture of different bases in DMF. Subsequent condensation of these derivatives with various acetophenones led to the synthesis of the corresponding N-benzylindolylchalcone derivatives. Notably, within this series of compounds,(E)-1-(4-fluorophenyl)-3-(1-(2-methylbenzyl)-1H-indol-3-yl)prop-2-en-1-one (S2R1) and (E)-1-(4-hydroxyphenyl)-3-(1-(3-methylbenzyl)- 1H-indol-3-yl)prop-2-en-1-one (S2R11) exhibited remarkable antitubercular activity, demonstrating minimal inhibitory concentrations values of 18 and 19 μg/mL, respectively.