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

Ragazzon, Patricia A.; Iley, Jim and Missailidis, Sotiris (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% (IG50) 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: Journal Item
Copyright Holders: 2009 Anticancer Research
ISSN: 1791-7530
Keywords: flavonoids; DNA binding; polynucleotides; triplex DNA; quadruplex DNA; cancer cell lines; UV; fluorescence spectroscopy; structure-activity relationship
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Other Departments > Other Departments
Other Departments
Item ID: 17527
Depositing User: James Iley
Date Deposited: 10 Aug 2009 09:44
Last Modified: 01 May 2019 13:16
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