New jatrophane diterpenoids from Euphorbia esula L

Euphorbia is the largest genus in the family Euphorbiaceae, comprising about 2000 species. Detailed study of the profile of all secondary metabolites could contribute to taxonomic subdivision of this complex genus. Hitherto many secondary metabolites with specific types of diterpene skeletons in the genus have been found to possess a number of interesting biological activities, including antiproliferative, antiviral, multidrug resistance (MDR) reversing activities [1–3]. Previously, six new diterpene of jatrophane type were isolated from Euphorbia esula by our group [4–6].

Results: In continuing our search for biologically active new compounds two new and two known jatrophane diterpenes were isolated from the aerial part of this plant. Compounds are hexa- and heptaesters of jatrophane polyols acylated with acetic, benzoic, isobutanoic and nicotinic acids. Compounds 1 and 2 are new natural products, but 3 and 4 were isolated earlier from Euphorbia salicifolia [7,8]. The structure elucidation was carried out by extensive spectroscopic analysis, including 1D and 2D NMR (¹H-¹H COSY, HSQC, and HMBC) and HRESIMS experiments. The stereochemistry of the compounds was studied by NOESY measurements. The isolated compounds were tested for their MDR-reversing activity on mouse lymphoma cells using a standard functional assay with Rhodamine 123 as a fluorescent substrate analogue of epirubicin. Verapamil was used as positive control.

Conclusions: On the basis of the diterpene composition, E. esula exhibits a close relationship with E. salicifolia, as they contain identical compounds, the main diterpene esulatin A, and 3 and 4. Moreover, the other compounds obtained from these two species differ only in the esterification. The isolated diterpenes possessing anti-MDR activity may prove to be useful lead compounds for inhibition of multidrug resistance of cancer cells and possible benefit could be exploited in combination chemotherapy of chemotherapy resistant cancer.

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