Abstract
Benz[b]oxepines 4a-g and 12-oxobenzo[c]phenanthridines 5a-d were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular radical cyclization reaction. Radical cyclization of O-vinyl compounds preferentially led to the 7-endo-trig cyclization pathway to the benz[b]oxepines and 12-oxobenzo[c]phenanthridines through 6-exo-trig path as minor products. Among the synthesized compounds, benz[b]oxepine derivative 4e exhibited potent in vitro cytotoxicity against three different tumor cell lines, as well as topoisomerase 1 inhibitory activity. A Surflex-Dock docking study was performed to clarify the topoisomerase 1 activity of 4e.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzoxepins / chemical synthesis*
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Benzoxepins / pharmacology
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Camptothecin / chemistry
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods
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DNA Topoisomerases, Type I / chemistry
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Drug Design
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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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HeLa Cells
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Humans
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Models, Chemical
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Molecular Conformation
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Phenanthrenes / chemical synthesis*
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Phenanthrenes / pharmacology
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Protein Binding
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Topoisomerase I Inhibitors
Substances
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Antineoplastic Agents
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Benzoxepins
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Enzyme Inhibitors
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Phenanthrenes
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Topoisomerase I Inhibitors
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phenanthridone
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DNA Topoisomerases, Type I
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Camptothecin