Background: Nuclear factor-kappaB (NF-kappaB) has been reported to
regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting
NF-kappaB may possess both anti-inflammatory and anticancer properties.
So there is a need to discover novel compounds which should not only be a potential
lead but also less toxic and cost effective.
Objectives: The aim of the study was to develop new synthetic anti-inflammatory and
cytotoxic agents targeting NF-kappaB.
Methods: Test compounds were synthesized and characterized by UV, IR, 1H-NMR,
13C-NMR and mass spectrometry. The synthesized compounds were evaluated for
in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in
carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using
propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2.
Result: Three series of compounds were synthesized and characterized by various spectroscopic techniques.
The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory
agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising
cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds
((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/
Conclusion: compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic
agents. In silico approach was in good tune with the wet lab experiments. The promising compounds
have shown to induce cell cycle arrest at G2/M Phase.