Abstract
Indenoisoquinolines and dihydroindenoisoquinolines have been synthesized possessing a nitro-substituted isoquinoline ring in an effort to explore the effects of electron-withdrawing substituents on biological activity. The in vitro anticancer activities of these molecules have been tested in the National Cancer Institute's screen of 55 cell lines. The compounds have also been tested for topoisomerase I (top1) inhibition. The results indicate that these substances are a potent class of top1 inhibitors with sub-micromolar cytotoxicity mean graph midpoints (MGM) and top1 inhibition equal to camptothecin.
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 / pharmacology
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Camptothecin / pharmacology
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Indenes / chemical synthesis
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Indenes / pharmacology
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Inhibitory Concentration 50
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Isoquinolines / chemical synthesis*
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Isoquinolines / 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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Indenes
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Isoquinolines
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Topoisomerase I Inhibitors
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isoquinoline
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Camptothecin