Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB

Title:Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB

Volume: 10 Issue: 2

Author(s): Kamlesh K. Naik, Sivakumar Thangavel and Afroze Alam

Affiliation:

Keywords: Anti-inflammatory, cell cycle analysis, cytotoxicity, flavanone, G2/M phase, nuclear factor-kappaB.

Abstract: 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/ mole.

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.

Cite this article as:

Naik K. Kamlesh, Thangavel Sivakumar and Alam Afroze, Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB, Recent Patents on Inflammation & Allergy Drug Discovery 2016; 10 (2) . https://dx.doi.org/10.2174/1872213X10666161114231625

DOI https://dx.doi.org/10.2174/1872213X10666161114231625	Print ISSN 1872-213X
Publisher Name Bentham Science Publisher	Online ISSN 2212-2710