On the mechanism of reductive activation in the mode of action of some anticancer drugs.
Bioactivation of a number of DNA-specific antitumor drugs depends on oxidoreduction. Bleomycin, neocarzinostatin and anthracycline glycosides are the best known among such drugs in terms of reductive activation processes. Their reduction results in short-lived radical or electrophilic intermediates attacking DNA stereospecifically. The physico-chemical properties of these drugs and the nature of DNA damage are reviewed. Models for DNA-intercalation, electron-donor systems involved in drug metabolisation, and the role of oxygen in radical reactions, are discussed in the light of recent reports.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001711:Biotransformation; D001761:Bleomycin / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D005609:Free Radicals; D009279:Naphthacenes / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D009353:Zinostatin / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D005609:Free Radicals; D009279:Naphthacenes; D001761:Bleomycin; D004247:DNA; D009353:Zinostatin; D010100:Oxygen