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.
Structure-activity relationships for euphocharacins A-L, a new series of jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein / G., Corea; E., Fattorusso; Lanzotti, Virginia; Motti, Riccardo; P. N., Simon; C., Dumontet; A. D., Pietro. - In: PLANTA MEDICA. - ISSN 0032-0943. - ELETTRONICO. - 70:(2004), pp. 657-665. [10.1055/s-2004-827191]
Structure-activity relationships for euphocharacins A-L, a new series of jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein
LANZOTTI, VIRGINIA;MOTTI, RICCARDO;
2004
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.