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 (<-0.10eV); 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 <5μM 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: 0.19μM) with good selectivity index (MIC(90)/CC(50): >1800). Thus, this study shows the potential of stereoelectronic property analysis in developing improved nitroaromatics as antitubercular agents.
Tawari
Nilesh R
NR
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
Bairwa
Ranjeet
R
Ray
M K
MK
Rajan
M G R
MG
Degani
Mariam S
MS
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011427:Propiophenones / Q000138:chemical synthesis* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000995:Antitubercular Agents; D005663:Furans; D007202:Indicators and Reagents; D011427:Propiophenones