Cytotoxic Naphthoquinones from Alkanna cappadocica
Cytotoxic Naphthoquinones from Alkanna cappadocica
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DOI：
10.1021/np900778j
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发表时间：
2010-05-01
影响因子：
5.1
通讯作者：
Bedir, Erdal
中科院分区：
文献类型：
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作者：
Sevimli-Gur, Canan;Akgun, Ismail H.;Bedir, Erdal
在从植物中发现新的抗癌剂，特别是来自Alkanna属的萘醌的持续计划中，研究了Alkanna cappadocica。生物测定引导分馏的二氯甲烷/甲醇（1：1）提取物的根导致四个新的和四个已知的萘醌的分离。已知的化合物是11-脱氧紫草素（1），β，β-二甲基丙烯酰紫草素（2），11-O-乙酰紫草素（3）和紫草素（4）。本文报道了新化合物5-O-甲基-11-脱氧紫草素（5）、8-O-甲基-11-脱氧紫草素（6）、5-O-甲基-11-O-乙酰紫草素（7）和5-O-甲基-β，β-二甲基丙烯酰紫草素（8）的结构。通过使用MIT测定，相对于12种人癌细胞系HT-29、MDA-MB-231、PC-3、AU565、Hep G2、LNCaP、MCF 7、HeLa、SK-BR-3、DU 145、Saos-2和Hep 3B以及两种正常细胞系VERO和3 T3，评价分离的化合物的细胞毒性。化合物7显示出显著的细胞毒性，IC 50值在0.09和14.07 μ M之间。在12种癌细胞系中的6种以及阳性对照阿霉素和依托泊苷中，它比其他化合物更有效。首次报道了单-O-甲基化紫草素衍生物及其细胞毒性。
In a continuing program to discover new anticancer agents from plants, especially naphthoquinones from the Alkanna genus, Alkanna cappadocica was investigated. Bioassay-guided fractionation of a dichloromethane/methanol (1:1) extract of the roots led to the isolation of four new and four known naphthoquinones. The known compounds are 11-deoxyalkannin (1), beta,beta-dimethylacrylalkannin (2), 11-O-acetylalkannin (3), and alkannin (4). The new compounds 5-O-methyl-11-deoxyalkannin (5), 8-O-methyl-11-deoxyalkannin (6), 5-O-methyl-11-O-acetylalkannin (7), and 5-O-methyl-beta,beta-dimethylacrylalkannin (8) were characterized by spectroscopic analyses (LC-ESIMS, 1D and 2D NMR). Cytotoxicity of the isolated compounds was evaluated versus 12 human cancer cell lines, HT-29, MDA-MB-231, PC-3, AU565, Hep G2, LNCaP, MCF7, HeLa, SK-BR-3, DU 145, Saos-2, and Hep 3B together with two normal cell lines, VERO and 3T3, by using the MIT assay. Compound 7 showed remarkable cytotoxicity with IC50 values between 0.09 and 14.07 mu M. It was more potent than the other compounds in six out of 12 cancer cell lines and the positive controls doxorubicin and etoposide. The mono-O-methylated alkannin derivatives and their cytotoxicities are reported for the first time.