Structure-activity studies of the binding of the flavonoid scaffold to DNA

Ragazzon, PA; Iley, J; Missailidis, S

Abstract

BACKGROUND:

Flavonoids have been shown to have a wide variety of biological activities and proven to be good scaffolds for the design of DNA-binding agents as anticancer therapeutics.
MATERIALS AND METHODS:

In structure-activity relationship studies, flavonoid derivatives were designed and synthesised through various organic synthesis protocols, resulting in novel or previously described molecules. These were studied by UV-Vis absorbance and fluorescence spectroscopy as well as competition dialysis for their binding to DNA isoforms. Their cytotoxic potential was assessed using MTS assays on MCF-7 breast cancer and CCRFCEM leukaemia cell lines.
RESULTS AND CONCLUSION:

Introduction of moieties such as chloride, nitrogen, acetoxy and methoxy groups did not help to improve binding affinity, but introduction of tertiary amines improved the binding 1,000-fold due to an improved interaction of the compound with the nucleic acid; replacement of oxygen by sulphur increased the binding 7-fold, possibly because sulphur being less electronegative than oxygen would allow the electrons of the molecule to interact more strongly with the nucleic acid. Inhibition of growth by 50% (IG(50)) values were moderate in breast and leukaemia cancer cell lines possibly due to the flavonoids interacting with other cellular components besides the nucleic acids.

Citation

Ragazzon, P., Iley, J., & Missailidis, S. (2009). Structure-activity studies of the binding of the flavonoid scaffold to DNA. Anticancer Research, 29(6), 2285-2293

• Journal Article Type: Article
• Publication Date: Jun 1, 2009
• Deposit Date: Jan 26, 2015
• Journal: Anticancer Research
• Print ISSN: 0250-7005
• Electronic ISSN: 1791-7530
• Publisher: International Institute of Anticancer Research
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 6
• Pages: 2285-2293
• Publisher URL: http://ar.iiarjournals.org/content/29/6/2285.full
• Related Public URLs: http://ar.iiarjournals.org/
• Additional Information: Funders : Open University