Nine cardiotonic steroids, six 17β-cardenolides (2, 4, 6-9) and three 17α-cardenolides (1, 3, 5) have been identified from the chloroform and chloroform-methanol exts. of Periploca graeca L. (Asclepiadaceae) stems. Among these, compd. 5 (I), the 17α-isomer of periplocin 6, was identified as a new compd. The antiproliferative effects of these compds. were tested in vitro in the hormone-independent prostate cancer cell line PC-3. Five of these compds., all 17β-isomers with a 14β-OH group and at least one sugar mol. (4, 6-9), showed a very strong antiproliferative effect, with IC50 values between 18 and 50 nM. Compd. 2, the only 17β-cardenolide aglycon, had an IC50 value of 0.6 μM, which is 13 to 16 times higher than the values found for the corresponding cardenolides with one or two sugars. The IC50 values found for the three 17α-isomers were significantly higher (5.4 and 7.3 μM), with IC50 ratios (17α-cardenolide/17β-cardenolide) of up to 192. In the 17α-cardenolide series the presence of a sugar unit does not seem to have a significant effect on the IC50 values. This is the first report showing a markedly different cytotoxicities between the 17α- and 17β-isomers in the cardenolide series.
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