Abstract
Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.
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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Animals
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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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Breast Neoplasms / drug therapy
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Cell Line, Tumor
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Cell Survival / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Mice
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Mice, Nude
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Neoplasms / drug therapy*
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Quinolones / chemical synthesis*
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Quinolones / chemistry
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Quinolones / pharmacology*
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Topoisomerase I Inhibitors*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Quinolones
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Topoisomerase I Inhibitors