Abstract
Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 microM. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic agents against the MCF-7 breast cancer cell line (IC50 = 0.36 and 0.48 microgram/mL, respectively) and the CAKI-1 renal cancer cell line (IC50 = 0.72 and 0.96 microgram/mL, respectively).
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / toxicity
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Breast Neoplasms
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Cell Survival / drug effects
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Colchicine / analogs & derivatives*
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Colchicine / chemical synthesis*
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Colchicine / chemistry
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Colchicine / toxicity
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / toxicity
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Female
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Humans
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Indicators and Reagents
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Kidney Neoplasms
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Kinetics
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Molecular Structure
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Structure-Activity Relationship
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Topoisomerase II Inhibitors*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Indicators and Reagents
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Topoisomerase II Inhibitors
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colchiceine
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Colchicine