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Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species
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 i...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Molecular Diversity Preservation International
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707043/ https://www.ncbi.nlm.nih.gov/pubmed/19597581 http://dx.doi.org/10.3390/md7020196 |
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author | Marshall, Kathryn M. Andjelic, Cynthia D. Tasdemir, Deniz Concepción, Gisela P. Ireland, Chris M. Barrows, Louis R. |
author_facet | Marshall, Kathryn M. Andjelic, Cynthia D. Tasdemir, Deniz Concepción, Gisela P. Ireland, Chris M. Barrows, Louis R. |
author_sort | Marshall, Kathryn M. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2707043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Molecular Diversity Preservation International |
record_format | MEDLINE/PubMed |
spelling | pubmed-27070432009-07-08 Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species Marshall, Kathryn M. Andjelic, Cynthia D. Tasdemir, Deniz Concepción, Gisela P. Ireland, Chris M. Barrows, Louis R. Mar Drugs Article 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. Molecular Diversity Preservation International 2009-05-25 /pmc/articles/PMC2707043/ /pubmed/19597581 http://dx.doi.org/10.3390/md7020196 Text en © 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Marshall, Kathryn M. Andjelic, Cynthia D. Tasdemir, Deniz Concepción, Gisela P. Ireland, Chris M. Barrows, Louis R. Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title | Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title_full | Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title_fullStr | Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title_full_unstemmed | Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title_short | Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species |
title_sort | deoxyamphimedine, a pyridoacridine alkaloid, damages dna via the production of reactive oxygen species |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707043/ https://www.ncbi.nlm.nih.gov/pubmed/19597581 http://dx.doi.org/10.3390/md7020196 |
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