PA Ragazzon
Structure-activity studies of the binding of the flavonoid scaffold to DNA
Ragazzon, PA; Iley, J; Missailidis, S
Authors
J Iley
S Missailidis
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 |