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

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

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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.

Item Type: Article
Themes: Health and Wellbeing
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Anticancer Research
Publisher: International Institute of Anticancer Research
Refereed: Yes
ISSN: 0250-7005
Related URLs:
Funders: Open University
Depositing User: PA Ragazzon
Date Deposited: 26 Jan 2015 13:58
Last Modified: 25 Jul 2018 21:18

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