Abstract
A series of substituted 9-aminoacridines is evaluated for antiproliferative activity toward pancreatic cancer cells. The results indicate that the compounds inhibit cell proliferation by inducing a G1-S phase arrest. A model is also developed that explains the molecular basis to inhibition through a DNA "threading" mechanism. We conclude that the drug-DNA complex formed blocks topoisomerase II binding and activity leading to catalytic inhibition of the enzyme and the induction of apoptosis and programmed cell death.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoacridines / chemical synthesis*
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Aminoacridines / chemistry
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Aminoacridines / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis*
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA / chemistry
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Drug Screening Assays, Antitumor
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Humans
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Models, Molecular
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Pancreatic Neoplasms
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Structure-Activity Relationship
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Topoisomerase II Inhibitors*
Substances
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Aminoacridines
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Antineoplastic Agents
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Topoisomerase II Inhibitors
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DNA