Abstract
Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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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 / pharmacology
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Cell Line, Tumor
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Crystallography, X-Ray
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DNA Cleavage / drug effects
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DNA Topoisomerases, Type I / chemistry
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Drug Screening Assays, Antitumor
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Humans
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Indenes / chemical synthesis*
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Indenes / chemistry
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Indenes / pharmacology
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Models, Molecular
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Molecular Structure
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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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Indenes
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Isoquinolines
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Topoisomerase I Inhibitors
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DNA Topoisomerases, Type I