TY - JOUR
T1 - Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead
AU - Corea, Gabriella
AU - Fattorusso, Ernesto
AU - Lanzotti, Virginia
AU - Taglialatela-Scafati, Orazio
AU - Appendino, Giovanni
AU - Ballero, Mauro
AU - Simon, Pierre Noël
AU - Dumontet, Charles
AU - Di Pietro, Attilio
PY - 2003/7/17
Y1 - 2003/7/17
N2 - The Mediterranean spurge Euphorbia dendroides L. afforded a series of 10 closely related jatrophane polyesters, nine of which are new, which served as a base for the establishment of structure-activity relationships within this class of P-glycoprotein inhibitors. The results, while pointing to the general role of lipophilicity for activity, also highlighted the relevance of the substitution pattern at the positions 2, 3, and 5, suggesting the involvement of this fragment in binding. The most powerful compound of the series, euphodendroidin D (4), outperformed cyclosporin by a factor of 2 to inhibit Pgp-mediated daunomycin transport.
AB - The Mediterranean spurge Euphorbia dendroides L. afforded a series of 10 closely related jatrophane polyesters, nine of which are new, which served as a base for the establishment of structure-activity relationships within this class of P-glycoprotein inhibitors. The results, while pointing to the general role of lipophilicity for activity, also highlighted the relevance of the substitution pattern at the positions 2, 3, and 5, suggesting the involvement of this fragment in binding. The most powerful compound of the series, euphodendroidin D (4), outperformed cyclosporin by a factor of 2 to inhibit Pgp-mediated daunomycin transport.
UR - http://www.scopus.com/inward/record.url?scp=0038155173&partnerID=8YFLogxK
U2 - 10.1021/jm030787e
DO - 10.1021/jm030787e
M3 - Article
SN - 0022-2623
VL - 46
SP - 3395
EP - 3402
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 15
ER -