Dip. Di Scienze del Farmaco, Università del Piemonte Orientale, l̥Largo Donegani 2/3, 28100 Novara, Italy.
Dip. di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, l̥SS 554, Km 4.5, 09042 Monserrato, Cagliari, Italy.
Chem Phys Lipids. 2021 Oct;240:105137. doi: 10.1016/j.chemphyslip.2021.105137. Epub 2021 Sep 14.
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.
类黄酮是多酚化合物的一个巨大类别，普遍存在于高等植物中，也存在于大多数天然来源的食品和饮料中。它们可以被视为饮食中的多酚，对人类和动物的生理机能具有多种促进健康的作用，具有广泛的生物医学和营养功能，如激活或抑制脂氧合酶和环氧化酶等酶的作用、致癌物的解毒作用和化学预防作用。从化学角度来看，这些芳香族化合物可以根据 C 环上芳香族 B 环的位置、不饱和程度和氧化程度、羟基的位置及其官能化，分为六个亚类。在类黄酮中，类异戊烯基化的类黄酮代表了自然界中一个独特的类别，其中 C-类异戊烯基化最为常见，而 O-类异戊烯基化则很少存在。由于生物利用度的增加，这种亲脂性官能团在类黄酮骨架的不同位置的存在有时会导致其生物活性的相关变化。鉴于类异戊烯基化类黄酮在自然界中的有限发生率，我们评估了从两种类黄酮，槲皮素和青蒿素，开始合成 C-和 O-类异戊烯基衍生物，以探索结构-活性关系。结果表明，类异戊烯基化显著增强了类黄酮在癌细胞 HeLa 中的细胞毒性作用，同时提高了它们影响细胞磷脂和脂肪酸组成的能力。青蒿素 C-类异戊烯基衍生物的细胞生物利用度显著增加。
