Abstract
DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 microM.
MeSH terms
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification*
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Antineoplastic Agents, Phytogenic / pharmacology
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DNA* / analysis
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DNA* / drug effects
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DNA* / metabolism
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Dose-Response Relationship, Drug
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Electrophoresis, Agar Gel
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Enzyme Inhibitors / pharmacology*
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Etoposide / pharmacology
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Oleanolic Acid / analogs & derivatives
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Oleanolic Acid / chemistry
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Oleanolic Acid / isolation & purification*
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Oleanolic Acid / pharmacology
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Pentacyclic Triterpenes
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Phyllanthus / chemistry*
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Plant Bark / chemistry
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Plants, Medicinal / chemistry*
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Plasmids
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Stereoisomerism
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors*
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Triterpenes / chemistry
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Triterpenes / isolation & purification*
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Triterpenes / pharmacology
Substances
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Antineoplastic Agents, Phytogenic
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Enzyme Inhibitors
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Pentacyclic Triterpenes
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors
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Triterpenes
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olean-12-en-3,15,24-triol
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olean-12-en-3,15-diol
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olean-12-en-3,24-diol
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Etoposide
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Oleanolic Acid
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betulin
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DNA
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lupeol