Effects of quercetin and artemetin prenylation on bioavailability and bioactivity

Flavonoids are a huge class of polyphenolic compounds ubiquitous in higher plants, in most food and beverages of natural origin. They could be considered as dietary phenols, which exert many health-promoting effects on human and animal physiology with a wide range of biomedical and nutritional functions such as activation or inhibition of enzymes like lipoxygenase and cyclooxygenase, the detoxification of carcinogens and chemoprevention. From a chemical point of view, these aromatic compounds can be divided in six subgroups depending on the position of aromatic B ring on C ring, the degree of unsaturation and oxidation, the position of hydroxyl groups and their functionalization. Between flavonoids, the prenylated ones represent a unique class occurring in nature where the C-prenylation is the most common, whereas O-prenylation is rarely present. The presence of this lipophilic functional group in different positions on the scaffold of flavonoids can sometimes lead to relevant changes in their biological activity due to an increased bioavailability. Capitalizing on the restricted incidence in nature of prenylated flavonoids, we have assessed the synthesis of C- and O-prenylated derivatives starting from two flavonoids, quercetin and artemetin, aimed at the exploration of structure-activity relationships. Results showed that prenylation significantly increased the cytotoxic effect of flavonoids in cancer HeLa cells, also improving their capacity to affect cell phospholipid and fatty acid composition. A marked cell bioavailability increase was demonstrated for the artemetin C-prenylated derivative.