Flavonoids and anticancer activity: Structure–activity relationship

Cancer is a multistage and heterogeneous disease caused by the accumulation of genetic and epigenetic changes. As polyphenols exhibit antitumor properties, they are considered to be potential drugs for therapeutic or chemopreventive purposes. Flavonoids from polyphenolic secondary metabolites have a wide spectrum of pharmacological activities such as anticancer, antiviral, antifungal, antibacterial, antioxidant, cardioprotective, immunomodulatory, and antiinflammatory. Anticancer activity mechanisms of flavonoids include inhibition of cell growth, cell proliferation, invasion, and metastasis as well as stimulation of apoptosis, and cell-cycle arrest. Flavonoids have a common C6-C3-C6 skeleton, which includes different substitution units to produce subclass compounds. The functionality and chemical structure of flavonoids affect their biochemical and pharmacological properties. For instance, isoprenoid fragment substitutions, binding position, and the number of isoprenoid-substituent fragments per molecule increase cytotoxicity, thereby exhibiting anticancer activity. In studies investigating the anticancer activities of tea polyphenols, it has been reported that galloylated catechins show a stronger antiproliferative effect and those in which EGCG has the most potent activity. In other studies, flavonoids containing 5-OH group in their structure have been reported to display a lower cytotoxic activity. In this chapter, selected flavonoids and their chemical structures and the relationship between these structures and their molecular mechanisms will be explained in terms of chemopreventive activity.