Enhancement of anticancer potential of polyphenols by covalent modifications.

As evidenced by a growing number of respective clinical trials, a promising and increasingly valued approach to cancer prevention is chemoprevention which is based on using synthetic, semisynthetic, or natural compounds with the aim of preventing, delaying, arresting, or reversing carcinogenesis. Research carried out in the last two decades indicates that natural polyphenols isolated from plants (as well as their derivatives and synthetic analogs) exhibit pleiotropic actions toward cancer cells and therefore they could be used in both cancer prevention and therapy. This review discusses selected covalent modifications of polyphenols as a means for increasing their anticancer potential in relation to the parent compounds. The modifications include hydroxylation, methylation, acylation, and galloylation, among others. They were demonstrated to enhance cytotoxic, pro-oxidant, antiproliferative, proapoptotic, proautophagic, and antimigratory activities of phenolics toward various cancer cell lines in vitro. Importantly, some derivatives proved to suppress tumor growth and metastasis in animal models more strongly than the parent compounds. Some of the above-mentioned covalent modifications were also shown to increase absorption and tissue distribution of tested phenolic compounds in vivo. Anticancer clinical trials with polyphenol derivatives therefore seem warranted.