Synthesis and biological evaluation of N-substituted indole chalcone derivatives as potent antitubercular agents

Abstract

The in vitro antitubercular activity of a new family of N-substituted indole chalcone analogues against Mycobacterium Tuberculosis H37Rv has been synthesized and evaluated. The synthesis of N-substituted indole chalcone derivatives, namely, 1-(2-oxo-2-phenylethyl)-1H-indole-3-carbaldehyde (S3I1), 1-(2-oxo-2-(p-tolyl)ethyl)-1H-indole-3-carbaldehyde (S3I2), 1-(2-(4-nitrophenyl)-2-oxoethyl)-1H-indole-3-carbaldehyde (S3I3), and 1-(2-(4-methoxyphenyl)-2-oxoethyl)-1H-indole-3-carbaldehyde (S3I4), was achieved by N-substitution of indole-3-carbaldehyde using potassium carbonate in DMSO. Subsequent condensation of these derivatives with various acetophenones led to the synthesis of the corresponding N-substituted indole chalcone derivatives. Notably, within this series of compounds, (E)-1-(4-hydroxyphenyl)-3-(1-(2-oxo-2-phenyl–ethyl)-1H-indol-3-yl)prop-2-en-1-one (S3R3) and (E)-1-(4-bromo-2-hydroxyphenyl)-3-(1-(2-oxo-2-phenyl–ethyl)-1H-indol-3-yl)prop-2-en-1-one (S3R8) exhibited remarkable antitubercular activity, demonstrating minimal inhibitory concentrations values of 06 and 07 µg/mL, respectively. Various spectroscopic methods were used to develop, synthesise, and characterize N-substituted indole chalcone. Hence, newly synthesized N-substituted indole chalcone derivatives act as a promising approach for the design of a new antitubercular moiety with strong antimicrobial agents.

Graphical Abstract