Abstract
Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC(50) values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.
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 / pharmacology*
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Cell Line, Tumor / drug effects
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DNA Topoisomerases, Type I / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Leukemia, Lymphoid / metabolism
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Leukemia, Lymphoid / pathology*
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Phenanthridines / chemical synthesis
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Phenanthridines / pharmacology*
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Structure-Activity Relationship
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Topoisomerase I Inhibitors*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Phenanthridines
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Topoisomerase I Inhibitors
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DNA Topoisomerases, Type I