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.
Habtemariam
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Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK. s.habtemariam@gre.ac.uk
Dagne
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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