Macrocyclic Diterpenoids from Euphorbia semiperfoliata

Appendino, Giovanni; Jakupovic, Sven; Tron, Gian Cesare; Jakupovic, Jasmin; Milon, Veronique; Ballero, Mauro

doi:10.1021/np970507w

Cited by 87 publications

(94 citation statements)

References 18 publications

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“…Assuming the S configuration at C-4, typical of all the members of the jatrophane family isolated to date (deduced by X-ray analysis of some derivatives) (Hohmann et al 1997), the absolute stereochemistry reported in structure 1 could be confidently assigned to euphodendroidin A. Moreover, it should be noted that the small value of J H-4/H-5 (1.2 Hz) has been correlated with a conformation of the 12-membered ring with the exomethylene group pointing outward and H-5 pointing inward (Appendino et al 1998). Accordingly, H-5 showed ROESY cross-peak with both OH-15 and with H-12.…”

Section: Jatrophane Diterpenes: Euphorbia Dendroidesmentioning

confidence: 82%

“…ROESY spectra determined the location of a acetate and a isobutyrate at C-2 and C-6, respectively. The relative configuration of terracinolide J (11) was investigated by measurement of scalar and dipolar couplings as well as by comparison with literature data (Appendino et al 1998;Marco et al 1996Marco et al , 1997, and has been found identical to that of all known terracinolides isolated to date.…”

Section: Modified Jatrophane Diterpenes: Euphorbia Dendroidesmentioning

confidence: 84%

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

et al. 2009

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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.

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Section: Jatrophane Diterpenes: Euphorbia Dendroidesmentioning

confidence: 82%

Section: Modified Jatrophane Diterpenes: Euphorbia Dendroidesmentioning

confidence: 84%

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

et al. 2009

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“…A jatrophane diterpene SJ23B (81, Figure 10) isolated from Euphorbia semiperfoliata [253] has shown a potential PKCα-mediated antiviral effect on HIV-1 infection and activation of latent HIV-1 gene expression, being 10-fold more potent than prostratin (70) [254].…”

Section: Other C1 Domain Ligandsmentioning

confidence: 99%

Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates

Gennäs

Talman²,

Yli‐Kauhaluoma³

et al. 2011

CTMC

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Protein kinase C (PKC) comprises a family of ten isoforms that play roles in diverse cellular processes such as proliferation, apoptosis and differentiation. PKC isoforms respond to Gprotein coupled receptor-and receptor tyrosine kinase-signaling via binding the second messenger diacylglycerol with C1 domains. Aberrant signaling through PKC isoforms and other C1 domain-containing proteins has been implicated in several pathological disorders.Drug discovery concerning C1 domains has exploited natural products and rationally designed compounds. Currently, molecules from several classes of C1 domain-binding compounds are in clinical trials; however, still more have the potential to enter the drug development pipeline. This review gives a summary of the recent developments in C1 domain-binding compounds.

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“…It is necessary to correct wrong configuration, also to clarify the interesting change of conformation in these types of diterpenes. 20 In Chinese traditional medicine XUSUIZI (Euphorbia lathyris), the main constituents are the lathyrane-type diterpenes, almost accounting for 5%, but the biological activities of macrocyclic lathyrane polyesters from E. lathyris have not been evaluated in depth before. 21,22 In our previous reports, configuration of several diterpenes have been investigated and rectified by X-ray diffraction.…”

Section: Introductionmentioning

confidence: 99%