Prooxidant action of knipholone anthrone: copper dependent reactive oxygen species generation and DNA damage.
Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological activities including in vitro antioxidant and cytotoxic properties. By using DNA damage as an experimental model, the comparative Cu(II)-dependent prooxidant action of these two compounds were studied. In the presence of Cu(II) ions, the antioxidant KA (3.1-200 microM) but not KP (6-384 microM) caused a concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by KA could be abolished by reactive oxygen species scavengers, glutathione and catalase as well as EDTA and a specific Cu(I) chelator bathocuproine disulfonic acid. In addition to Cu(II) chelating activity, KA readily reduces Cu(II) to Cu(I). Copper-dependent generation of reactive oxygen species and the subsequent macromolecular damage may be involved in the antimicrobial and cytotoxic activity of KA.
Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK. s.habtemariam@gre.ac.uk
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D000873:Anthracenes / Q000737:chemistry*; D000880:Anthraquinones / Q000737:chemistry / Q000633:toxicity; D000975:Antioxidants / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D016877:Oxidants / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D000095322:Anthrones
D000873:Anthracenes; D000880:Anthraquinones; D000975:Antioxidants; D002614:Chelating Agents; D003300:Copper; D004247:DNA; D004278:DNA, Superhelical; D016166:Free Radical Scavengers; D016877:Oxidants; D017382:Reactive Oxygen Species; C403586:knipholone; C543143:knipholone anthrone; D000095322:Anthrones