Bioassay-guided fractionation of an ethanol extract obtained from the Madagascar plant Elaeodendron sp. led to the isolation of two new cardenolides, elaeodendrosides T and U (1 and 2). The structures of the new compounds were elucidated using 1D and 2D NMR experiments, and mass spectrometry. Compounds 1, 3, 4, and 5 showed significant antiproliferative activity against A2780 human ovarian cancer cells with IC 50 values of 0.085, 0.019, 0.19, and 0.10 µM, respectively, while compounds 2 and 6 were less active.In our continuing search for bioactive molecules from the Madagascar rainforests as part of an International Cooperative Biodiversity Group (ICBG) program, 1 we obtained an EtOH extract of the wood of Elaeodendron sp. (Celastraceae). This extract (MG 3232) showed antiproliferative activity against the A2780 ovarian cancer cell line with an IC 50 value of 7.6 µg/mL. The extract was selected for bioassay-guided fractionation based on its activity, and also on the absence of any previous chemical investigation of the species.There are ca. forty species in the genus Elaeodendron from the Mexican coast, Bermuda, Africa, Madagascar (incl. Mascarene), India, Melanesia, and Australia. 2 The plants in this genus are usually glabrous trees or shrubs, 2 and flavonoids, 3 terpenoids, 4 and cardenolides 5 have been isolated from them. Cardenolides are also prominent cardioactive secondary metabolites of many medicinal plants belonging to the Apocynaceae (Nerium, Strophanthus, Thevetia), Asclepiadaceae (Periploca, Calotropis, Xysmalobium), Scrophulariaceae (Digitalis), Ranunculaceae (Adonis), and Convallariaceae families (Convallaria, Speirantha). 6 The cytotoxicity of cardenolides as well as their cardiac activity have been widely studied. 7An EtOH extract of the woods (MG 3232) of Elaeodendron sp. was subjected to liquid-liquid partitioning to give an active CH 2 Cl 2 fraction with an IC 50 value of 0.3 µg/mL in the A2780 *To whom correspondence should be addressed. Tel: (540) assay. Activity-guided separation of this fraction by passage over a C 18 SPE column yielded three subfractions, and subjection of the active second subfraction to further purification using C 18 HPLC led to the isolation of the two new compounds 1 and 2, and the four known compounds elaeodendroside B (3), 5f elaeodendroside F (4), 5f elaeodendroside G (5), 5f and (2α,3β,14β)-trihydroxy-3-O-(4-deoxy-3-O-methyl-α-L-erythro-pentopyranosyl)-card-4,20 (22)-dienolide (6). 5g Here we report the structures of the two new compounds elaeodendroside T (1) and U (2) as well as the antiproliferative activity of all the isolates.Compound 1 was obtained as a white powder. Its HRFABMS (positive-ion mode) exhibited a quasimolecular ion peak at m/z 589.2962, consistent with a molecular composition of C 32 H 45 O 10 (calcd 589.3013). The 13 C NMR spectrum of compound 1 contained 32 signals, which were assigned to one methoxy, one acetoxy, three methyls, eight methylenes, eleven methines, and eight quaternary carbons based on its 1 H NMR and HSQC spectra...
