Abstract
In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 microM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds.
2010 Elsevier Masson SAS. All rights reserved.
Publication types
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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 / metabolism
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cross-Linking Reagents / chemical synthesis
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Cross-Linking Reagents / chemistry
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Cross-Linking Reagents / metabolism
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Cross-Linking Reagents / pharmacology
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DNA / chemistry
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DNA / metabolism
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DNA Topoisomerases, Type II / metabolism
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Humans
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Topoisomerase II Inhibitors / chemical synthesis
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Topoisomerase II Inhibitors / chemistry
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Topoisomerase II Inhibitors / metabolism
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Topoisomerase II Inhibitors / pharmacology
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Xanthones / chemical synthesis*
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Xanthones / chemistry
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Xanthones / metabolism
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Xanthones / pharmacology*
Substances
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Antineoplastic Agents
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Cross-Linking Reagents
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Topoisomerase II Inhibitors
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Xanthones
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DNA
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xanthone
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DNA Topoisomerases, Type II