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.

Key words

Euphorbiaceae - Euphorbia characias - diterpenes - jatrophanes - P-glycoprotein - SAR studies

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