Abstract
The replacement of 1,3-dihydroxy-2-propylamino moiety at the N6-position of edotecarin (1) by arylmethylamino groups yielded a number of more potent topoisomerase I inhibitors with better cytotoxic (CTX) activities in vitro than edotecarin. Among them, the three most potent pyridylmethyl analogues, compounds 22g, 22m, and 23c, showed better antitumor activities against MKN-45 human stomach cancer or MX-1 human breast cancer xenografted mice than those of edotecarin. Furthermore, compounds 22m and 23c exhibited complete response against MX-1 cells implanted in mice.
MeSH terms
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Amines / chemistry*
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology
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Carbazoles / chemistry*
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Cell Line, Tumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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Hydrocarbons, Aromatic / chemistry
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Mice
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Pyridines / chemistry
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Stomach Neoplasms / drug therapy
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Stomach Neoplasms / pathology
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Structure-Activity Relationship
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Topoisomerase I Inhibitors*
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Xenograft Model Antitumor Assays
Substances
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Amines
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Antineoplastic Agents
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Carbazoles
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Enzyme Inhibitors
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Hydrocarbons, Aromatic
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Pyridines
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Topoisomerase I Inhibitors
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edotecarin