Abstract
The Mediterranean spurge Euphorbia characias L. afforded twelve new diterpenes based on a jatrophane skeleton named euphocharacins A-L. Their chemical structures were elucidated by extensive nuclear magnetic resonance and mass spectrometry methods. Euphocharacins A-L were tested as inhibitors of the daunomycin-efflux activity of P-glycoprotein from cancer cells. The results were used to extend the structure-activity relationship established for this class of compounds, highlighting the positive effects of propyl and benzoyl groups at positions 3 and 9, respectively, and evidencing the negative effect of a free hydroxyl group at position 2. Among the tested compounds, euphocharacins C and I showed an activity higher than cyclosporin to inhibit Pgp-mediated daunomycin transport.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antineoplastic Agents, Phytogenic / therapeutic use
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / metabolism
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Diterpenes / administration & dosage
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Diterpenes / chemistry
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Diterpenes / pharmacology*
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Diterpenes / therapeutic use
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Euphorbia*
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Humans
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Phytotherapy*
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Plant Extracts / administration & dosage
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Plant Extracts / therapeutic use
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Structure-Activity Relationship
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents, Phytogenic
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Diterpenes
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Plant Extracts