College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
Arch Pharm Res. 2010 Sep;33(9):1347-53. doi: 10.1007/s12272-010-0908-8. Epub 2010 Oct 9.
A bioassay-guided fractionation of the CH(2)Cl(2) extract of Selaginella tamariscina yielded six sterols 1-6 such as (4α, 5α)-4, 14-dimethylcholest-8-en-3-one (1), ergosta-4, 6, 8(14), 22-tetraene-3-one (2), ergosterol endoperoxide (3), 7β-hydroxycholesterol (4), 7β-hydroxysitosterol (5), and 7α-hydroxysitosterol (6). The structures of isolated compounds were determined using spectroscopic methods. Among these isolates, compounds 2-5 showed potent cytotoxicity against five human tumor cells, while compounds 1 and 6 did not. In the case of compounds 1 and 2, 3-oxo sterol derivatives, compound 1 was inactive, but compound 2 showed potent cytotoxicity. In addition, compound 5 exhibited potent cytotxicity, but, compound 6 which is the 7-epimer of compound 5 was weakly active against tumor cell lines. Therefore, in the case of oxysterol derivatives, the cytotoxicity appeared to be affected by the structural differences, i.e. the configuration of hydroxyl group and the number of conjugated double bond. Taken all together, the present study isolated six sterols from S. tamariscina for the first time based on a bioassay-guided fractionation and indicated that isolated oxysterols could exhibit the cytotoxic effects against tumor cells, suggesting that S. tamariscina might be a promising candidate for the development of anticancer agents.
从卷柏 CH(2)Cl(2)提取物中进行生物测定指导的分段得到了六种甾醇 1-6，如(4α,5α)-4,14-二甲基胆甾-8-烯-3-酮(1)、麦角甾-4,6,8(14),22-四烯-3-酮(2)、麦角甾-4,6,8(14),22-四烯-3-酮过氧化物(3)、7β-胆甾醇(4)、7β-谷甾醇(5)和 7α-谷甾醇(6)。使用光谱方法确定了分离化合物的结构。在这些分离物中，化合物 2-5 对五种人肿瘤细胞表现出强烈的细胞毒性，而化合物 1 和 6 则没有。在化合物 1 和 2 中，3-氧代固醇衍生物，化合物 1 没有活性，但化合物 2 表现出强烈的细胞毒性。此外，化合物 5 表现出强烈的细胞毒性，但化合物 6 是化合物 5 的 7-差向异构体，对肿瘤细胞系的活性较弱。因此，在氧化固醇衍生物的情况下，细胞毒性似乎受到结构差异的影响，即羟基的构型和共轭双键的数量。综上所述，本研究首次基于生物测定指导的分段从卷柏中分离出六种甾醇，并表明分离出的氧化固醇可能对肿瘤细胞表现出细胞毒性作用，表明卷柏可能是开发抗癌药物的有前途的候选物。
