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Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East Rm. 201, Salt Lake City, Utah 84112, USA
Current address: Department of Surgery, University of Melbourne, Austin Health, Studley Rd, Heidelberg, Victoria 3084, Australia
Department of Medicinal Chemistry, University of Utah, 30 South 2000 East Rm. 301, Salt Lake City, Utah 84112, USA
Current address, Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London WC1N 1AX, UK
The Marine Science Institute, University of Philippines, Velasquez Street, Dilman, Quezon City 1101, Philippines
* Author to whom correspondence should be addressed.
Received: 5 February 2009; in revised form: 12 May 2009 / Accepted: 16 May 2009 / Published: 25 May 2009
Abstract: Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity.
Keywords: deoxyamphimedine; neoamphimedine; amphimedine; pyridoacridine; reactive oxygen species
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Marshall, K.M.; Andjelic, C.D.; Tasdemir, D.; Concepción, G.P.; Ireland, C.M.; Barrows, L.R. Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species. Mar. Drugs 2009, 7, 196-209.
Marshall KM, Andjelic CD, Tasdemir D, Concepción GP, Ireland CM, Barrows LR. Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species. Marine Drugs. 2009; 7(2):196-209.
Marshall, Kathryn M.; Andjelic, Cynthia D.; Tasdemir, Deniz; Concepción, Gisela P.; Ireland, Chris M.; Barrows, Louis R. 2009. "Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species." Mar. Drugs 7, no. 2: 196-209.