Structure-activity relationships for euphocharacins A-L, a new series of jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein.

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.

• Authors: Gabriella Corea, Ernesto Fattorusso, Virginia Lanzotti, Riccardo Motti, Pierre-Noël Simon, Charles Dumontet, Attilio Di Pietro
• Journal: Planta medica (Planta Med) Vol. 70 Issue 7 Pg. 657-65 (Jul 2004) ISSN: 0032-0943 [Print] Germany
• PMID: 15254859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Diterpenes
• Plant Extracts

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology, therapeutic use)
• Cell Line, Tumor (drug effects, metabolism)
• Diterpenes (administration & dosage, chemistry, pharmacology, therapeutic use)
• Euphorbia
• Humans
• Phytotherapy
• Plant Extracts (administration & dosage, chemistry, pharmacology, therapeutic use)
• Structure-Activity Relationship