The relation between the chemical structure of flavonoids and their estrogen-like activities

Estrogens are steroid hormones exhibiting a broad range of physiological activities, which are important in the homeostatic regulation of many cellular and biochemical events. Estradiol (E(2)) is an estrogen which is active in the development of the mammary glands and the uterus, in the maintenance of pregnancy and bone density, in protection from cardiovascular diseases, and in the relief of menopausal symptoms. However, it can also stimulate malignant growths, and hence contribute to the development of estrogen-dependent tumors, such as cancer of the breast and uterus. Phytoestrogens are plant-derived chemicals with estrogen-like activities, which could have a beneficial role in humans against estrogen deficiency. Several studies relate the lower incidence of estrogen deficiency-related disease among women in the Eastern word to a diet rich in phytoestrogens. This compound comprises a variety of structurally diverse chemicals, with flavonoids as their largest group. In the present review we summarize knowledge gained on the relationship between the structure of flavonoids to their ability to mimic estrogen activity, together with the methods adapted to perform these studies. The methods reviewed are qualitative and quantitative measurements of the estrogen-like activities of phytoestrogens, superposition analysis, docking analysis and quantitative structure-activity relationship (QSAR) models. The potential of various new flavonoid derivatives in hormone replacment therapy is discussed.