NDLI: Jatrophane diterpenes from Euphorbia spp. as modulators of multidrug resistance in cancer therapy

Content Provider	Springer Nature Link
Author	Corea, G. Di Pietro, A. Dumontet, C. Fattorusso, E. Lanzotti, V.
Copyright Year	2009
Abstract	A phytochemical investigation of the aerial parts of Euphorbia spp., considered one of the most common elements of Mediterranean landascape, led to the isolation of a large number of bioactive plant metabolites, belonging to the diterpenes family. Above all, over seventy jatrophane, modified jatrophane, segetane, pepluane, and paraliane diterpenoids, fifty of them reported for the first time, were extracted, purified and characterized from Euphorbia dendroides, Euphorbia characias, Euphorbia peplus, Euphorbia paralias and Euphorbia helioscopia. These compounds showed interesting pharmacological activities. In particular, jatrophanes, modified jatrophanes and lathyranes exhibited a potent inhibitory activity against P-glycoprotein (Pgp), a membrane protein that confers cellular ability to resist lethal doses of certain cytotoxic drugs by pumping them to the outside, thus resulting in a reduced cytotoxicity. Among the others, our chemical survey led to isolation of the most powerful inhibitors of daunomycin-efflux activity isolated to date for this class of inhibitors, named euphodendroidin D and pepluanin A. Their efficiency was found to be at least two-fold higher than the conventional modulator cyclosporin A, taken as a reference. In addition, the isolation of a high number of natural structurally-related analogues allowed us to perform Structure Activity Relationship (SAR) studies, without any chemical modification, which gave information on the key pharmacophoric elements of these new class of promising drugs. A further set of diterpene analogues, very recently isolated from sun spurge, E. helioscopia, individually investigated for their Pgp- and BCRP-inhibiting properties, appeared to be specific inhibitors of Pgp since they showed no significant activity against BCRP, thus resembling to the third-generation class of specific MDR inhibitors.
Starting Page	431
Ending Page	447
Page Count	17
File Format	PDF
ISSN	15687767
Journal	Phytochemistry Reviews
Volume Number	8
Issue Number	2
e-ISSN	1572980X
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-03-21
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Euphorbia Diterpenes Jatrophanes Modified jatrophanes Lathyranes Multidrug resistance Pgp BCRP Third generation inhibitors Chemistry/Food Science Organic Chemistry Biochemistry Plant Genetics & Genomics Plant Sciences
Content Type	Text
Resource Type	Article
Subject	Plant Science Biotechnology

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