Abstract
Indenoisoquinolines with lactam substituents such as ethylamino, propylamino, and butylamino have previously demonstrated potent biological activity, but an optimal length has never been established. In the present study, a series of simplified indenoisoquinoline analogues possessing a linker spacing of 0-12 carbon atoms between the lactam nitrogen and the terminal amino group have been prepared, determining that 2-4-atom lengths are optimal for topoisomerase I inhibition and cytotoxicity. Using these lengths, analogues were prepared with the amino group and portions of the linker replaced by a pyridine ring. A three-carbon spacer within the pyridine series still demonstrated potent topoisomerase I inhibition.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Humans
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Indenes / chemical synthesis*
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Indenes / chemistry
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Indenes / pharmacology
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Lactams / chemical synthesis*
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Lactams / chemistry
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Lactams / pharmacology
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Models, Molecular
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Pyridines / chemistry
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Topoisomerase I Inhibitors*
Substances
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Antineoplastic Agents
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Indenes
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Isoquinolines
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Lactams
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Pyridines
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Topoisomerase I Inhibitors