Spera Daniela, Siciliano Tiziana, De Tommasi Nunziatina, Braca Alessandra, Vessières Anne
Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Pisa, Italy.
Planta Med. 2007 Apr;73(4):384-7. doi: 10.1055/s-2007-967133. Epub 2007 Mar 15.
Nine cardiotonic steroids, six 17beta-cardenolides (2, 4, 6-9) and three 17alpha-cardenolides (1, 3, 5) have been identified from the chloroform and chloroform-methanol extracts of Periploca graeca L. (Asclepiadaceae) stems. Among these, compound 5, the 17alpha-isomer of periplocin 6, was identified as a new compound. The antiproliferative effects of these compounds were tested in vitro in the hormone-independent prostate cancer cell line PC-3. Five of these compounds, all 17beta-isomers with a 14beta-OH group and at least one sugar molecule (4, 6-9), showed a very strong antiproliferative effect, with IC50 values between 18 and 50 nM. Compound 2, the only 17beta-cardenolide aglycone, had an IC50 value of 0.6 microM, 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 17alpha-isomers were significantly higher (5.4 and 7.3 microM), with IC50 ratios (17alpha-cardenolide/17beta-cardenolide) of up to 192. In the 17alpha-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 17alpha- and 17beta-isomers in the cardenolide series.
从杠柳（萝摩科）茎的氯仿提取物和氯仿 - 甲醇提取物中已鉴定出九种强心甾体，六种17β - 强心甾烯类（2,4,6 - 9）和三种17α - 强心甾烯类（1,3,5）。其中，化合物5，即杠柳毒苷6的17α - 异构体，被鉴定为一种新化合物。在激素非依赖性前列腺癌细胞系PC - 3中对这些化合物的抗增殖作用进行了体外测试。这些化合物中的五种，均为具有14β - OH基团和至少一个糖分子的17β - 异构体（4,6 - 9），显示出非常强的抗增殖作用，IC50值在18至50 nM之间。化合物2，唯一的17β - 强心甾烯苷元，IC50值为0.6 microM，比具有一个或两个糖的相应强心甾烯类化合物的值高13至16倍。三种17α - 异构体的IC50值明显更高（5.4和7.3 microM），IC50比率（17α - 强心甾烯类/17β - 强心甾烯类）高达192。在17α - 强心甾烯类系列中，糖单元的存在似乎对IC50值没有显著影响。这是首次报道强心甾烯类系列中17α - 和17β - 异构体之间细胞毒性存在明显差异。
