Antiarol Cinnamate and Africanoside, a Cinnamoyl Triterpene and a Hydroperoxy-cardenolide from the Stem Bark of Antiaris africana

From the methanol extract of the stem bark of the African tree Antiaris africana Engler, two new bioactive metabolites were isolated, namely, the alpha-amyrin derivative 1,beta,11 alpha-dihydroxy-3 beta-cinnamoyl-alpha-amyrin (antiarol cinnamate, 1) and a cardiac glycoside, 3 beta-O-(alpha-L-rhamnopyranosyl)-14 beta-hydroperoxy-5 beta-hydroxy-19-oxo-17 beta- card-20(22)-enolide (africanoside, 2a), together with the known compounds P-amyrin and its acetate, beta-sitosterol and its 3-O-beta-D-glucopyranoside, friedelin, ursolic and oleanolic acid, 19-norperiplogenin, strophanthidol, strophanthidinic acid, periplogenin (3a), 3-epiperiplogenin, strophanthidin (3b) and 3,3'-dimethoxy-4'-O-beta-D-xylopyronosyl-ellagic acid. Their structures were established on the basis of their spectroscopic data and by chemical methods, while 3a was additionally confirmed by X-ray crystal structure analysis. The aglycone moiety possessing a hydroperoxy group was found for the first time in cardenolides. Compounds 1 and 2a showed no activity against bacteria, fungi, and microalgae; however, the crude extract exhibited a high toxicity against Artemia sauna and a selective antitumor activity against human tumor cell lines. Africanoside (2a) effected a concentration-dependent inhibition of tumor cell growth with a mean IC(50) value of 5.3 nM.