Free radical formation by antitumor quinones

Quinones are among the most frequently used drugs to treat human cancer. All of the antitumor quinones can undergo reversible enzymatic reduction and oxidation, and form semiquinone and oxygen radicals. For several antitumor quinones enzymatic reduction also leads to formation of alkylating species but whether this involves reduction to the semiquinone or the hydroquinone is not always clear. The antitumor activity of quinones is frequently linked to DNA damage caused by alkylating species or oxygen radicals. Some other effects of the antitumor quinones, such as cardiotoxicity and skin toxicity, may also be related to oxygen radical formation. The evidence for a relationship between radical formation and the biological activity of the antitumor quinones is evaluated.