Abstract
The 2,2-dimethyl-2H-pyran-derived alkaloids acronycine and its demethylated congeners were prepared in three steps from anthranilic acid and phloroglucinol. The phenylboronic acid-mediated interamolecular cyclization reaction of 1,3-dihydroxyacridone and 3-methylbut-2-enal was employed as a key step, which was also applied to the synthesis of related cytotoxic benzo[b]acronycine. Inhibitory activities of the compounds prepared on topoisomerase I and II as well as their cytotoxicities were evaluated. Cytotoxicity of 2 is closely related to the strong inhibitory activity against topo II at 20 microM level.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acronine / analogs & derivatives*
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Acronine / chemical synthesis
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Acronine / pharmacology
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / pharmacology
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Camptothecin / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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DNA / drug effects
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Drug Screening Assays, Antitumor
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Etoposide / pharmacology
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Humans
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Indicators and Reagents
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors
Substances
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Antineoplastic Agents, Phytogenic
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Indicators and Reagents
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors
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benzo(b)acronycine
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Etoposide
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DNA
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Acronine
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Camptothecin