School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Eur J Med Chem. 2011 Aug;46(8):3420-7. doi: 10.1016/j.ejmech.2011.05.006. Epub 2011 May 12.
We recently discovered that 5, 8-O-dimethyl acylshikonin derivatives displayed the selectivity towards MCF-7 and no toxicity to normal cells. Herein, a series of the corresponding 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized starting from shikonin. In vitro evidence of the cytotoxicities indicated that most of thecompounds were more active than or comparative to shikonin and retained the selectivity against MCF-7, MDA-MB-231 besides no toxicity in the normal cells. Also, in vivo anticancer activity of the positional isomers 5p, 6c further showed that 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were more active than their corresponding 2-isomers. Thus, we may conclude that the position of the side chain of shikonin attached to 5,8-dimethoxy -1,4-naphthoquinone is associated with the antitumor activity.
我们最近发现，5,8-O-二甲基酰基紫草素衍生物对 MCF-7 具有选择性，对正常细胞无毒。在此，我们从紫草素出发，合成了一系列相应的 5,8-O-二甲基酰基紫草素衍生物的 6-异构体。体外细胞毒性实验表明，大多数化合物比紫草素更具活性或相当，并且对 MCF-7、MDA-MB-231 具有选择性，对正常细胞没有毒性。此外，位置异构体 5p、6c 的体内抗癌活性进一步表明，5,8-O-二甲基酰基紫草素衍生物的 6-异构体比其相应的 2-异构体更具活性。因此，我们可以得出结论，紫草素连接到 5,8-二甲氧基-1,4-萘醌的侧链位置与抗肿瘤活性有关。
