A few considerations on quinones as antitumor agents

Although a number of quinones represent important antitumor drugs, the role of the quinone ring in this activity does not seem to be established. Active quinones are relatively large molecules which either possess a large quinoid system, in particular that of anthraquinone, or contain the benzoquinone ring imbedded in a larger molecular skeleton. Simple small quinones have little if any clinical utility. The cellular target of quinones is DNA. Drugs having a large anthraquinone ring interact with DNA essentially by intercalation, small quinones imbedded in a larger molecular framework react with DNA essentially by covalent bond formation which, however, does not involve the quinone ring itself. The establishment of the adducts seems to necessitate the activation of the drugs, which may be produced by protonation or, better, by bioreductive alkylation. There does not seem to be any straightforward correlation between the antitumor potency and the one‐electron reduction potential of the quinone–semiquinone couples. The generation of free radicals upon the reoxidation of the hydroquinone moiety of DNA‐bound quinones may cause single‐strand breaks in DNA, but these are also produced by intercalating drugs which cannot undergo bioreductive alkylation. Analogs of active quinones which lack the quinone system may also manifest antitumor activity. The determination of the specific significance of the quinone system in antitumor activity needs thus further investigation.