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新型香叶基香叶基化香豆素衍生物的抗癌活性。

Pancreatic anticancer activity of a novel geranylgeranylated coumarin derivative.

机构信息

Department of Chemistry, Wellesley College, Wellesley, MA 02481, USA.

出版信息

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5770-3. doi: 10.1016/j.bmcl.2011.08.005. Epub 2011 Aug 8.

Abstract

A series of hydroxycoumarin derivatives has been synthesized and evaluated against human pancreatic PANC-1 cancer cells under nutrient-deprived conditions. Several compounds exhibited 100% preferential cytotoxicity at low micromolar concentrations under nutrition starvation, and showed no cytotoxicity under nutrient-rich conditions. In this study, a novel geranylgeranylated ether coumarin derivative 9 was found to exhibit the highest cytotoxic activity of 6.25 μM within 24h. The preferential anti-tumor activity exhibited by compound 9 against PANC-1 under low oxygen and nutrient environment illustrates its great potential as a promising lead structure for the development of novel agents to combat pancreatic cancer.

摘要

已合成了一系列羟基香豆素衍生物,并在营养缺乏条件下对人胰腺 PANC-1 癌细胞进行了评估。在营养饥饿状态下,几种化合物在低微摩尔浓度下表现出 100%的选择性细胞毒性,而在营养丰富的条件下则没有细胞毒性。在这项研究中,发现一种新型的香叶基香叶基醚香豆素衍生物 9 在 24 小时内以 6.25 μM 的浓度表现出最高的细胞毒性。化合物 9 在低氧和低营养环境下对 PANC-1 表现出的选择性抗肿瘤活性表明,它作为一种有前途的先导结构,具有开发新型药物治疗胰腺癌的巨大潜力。

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