Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 460, Issue 1, Pages 1-9Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2007.02.003
Keywords
flavonoids; metabolites; structure-activity relationships; cytotoxicity; lymphocytes; anticancer; EC50; solubility maximum
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The aim of this study was to identify structure elements in flavonoids that are associated with enhanced cytotoxic activity. We determined the cytotoxicity (EC50) of 23 different flavonoids, including O-methylated and glucuronidated metabolites, on the human leukemia cell line Jurkat E6-1 by analyzing cell death triggered after 24 and 48 h. By comparing the cytotoxicity of selected molecules that differ in only one structure element, we identified several structure-function relationships associated with enhanced cytotoxicity, including the presence of a 2-3 double bond, the presence of a 4-carbonyl group and ortho- compared to meta-hydroxylation in the B ring. Molecules with a 3-hydroxyl group exhibited significantly lower cytotoxicity than their non-hydroxylated counterparts. O-Methylation and glucuronidation were associated with a significant increase in cytotoxicity, suggesting that metabolites found in vivo are more active than unmodified flavonoids. We identified the solubility maximum of the tested flavonoids in culture medium and found a negative correlation between maximum solubility and cytotoxicity. The results of our study may help to identify novel flavonoid structures with optimized cytotoxic activity to be tested for anti-cancer treatment. (c) 2007 Elsevier Inc. All rights reserved.
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