Design, synthesis, and biological evaluation of 4-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives as potent antitubercular agents

Based on stereoelectronic feature analysis using density functional theory (DFT) at B3LYP/3-21∗G level, a series of 4-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives with low LUMO energies (<−0.10 eV); concentrated over the nitro group, furan moiety and α,β-unsaturated carbonyl bridge were envisaged as potential antitubercular agents. The target compounds were prepared by condensation of 5-nitro-2-furaldehyde with various ketones under acidic condition. The compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H37Rv and their cytotoxicity in VERO cell line. Several synthesized compounds showed good antitubercular activity of <5 μM along with low cytotoxicity. In particular, compound ((E)-3-(5-nitrofuran-2-yl)-1-(4-(piperidin-1-yl)phenyl)prop-2-en-1-one) (3v) was found to be very potent (MIC: 0.19 μM) with good selectivity index (MIC90/CC50: >1800). Thus, this study shows the potential of stereoelectronic property analysis in developing improved nitroaromatics as antitubercular agents.

Graphical abstractBased on stereoelectronic feature analysis using density functional theory (DFT) at B3LYP/3-21∗G level, a series 4-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives were envisaged as potential antitubercular agents. As expected, synthesis and biological evaluation showed that target compounds were potent inhibitors of Mycobacterium tuberculosis. Thus, this study shows the potential of stereoelectronic property analysis in developing improved nitroaromatics as antitubercular agents.Figure optionsDownload full-size imageDownload as PowerPoint slide