Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species

Marine Drugs

Kathryn M. Marshall²  Cynthia D. Andjelic²  Deniz Tasdemir¹  Gisela P. Concepción³  Chris M. Ireland¹ 

[1] Department of Medicinal Chemistry, University of Utah, 30 South 2000 East Rm. 301, Salt Lake City, Utah 84112, USA; E-Mail:;Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East Rm. 201, Salt Lake City, Utah 84112, USA; E-Mail:;The Marine Science Institute, University of Philippines, Velasquez Street, Dilman, Quezon City 1101, Philippines; E-Mails:

关键词: deoxyamphimedine;    neoamphimedine;    amphimedine;    pyridoacridine;    reactive oxygen species;   

DOI  :  10.3390/md7020196

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.