Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells.
Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells.
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DOI：
10.1021/acs.jnatprod.5b00908
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发表时间：
2016-03-25
影响因子：
5.1
通讯作者：
Mooberry SL
中科院分区：
文献类型：
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作者：
Shaffer CV;Cai S;Peng J;Robles AJ;Hartley RM;Powell DR;Du L;Cichewicz RH;Mooberry SL
仍然迫切需要用于治疗晚期和转移性前列腺癌的更有效的疗法。三种德克萨斯州的原生植物产生了三种新的和三种已知的化合物，它们对前列腺癌细胞具有抗增殖和细胞毒性活性，IC 50值在1.7-35.0 µM范围内。从Gochnatia hypoleuca中分离得到一个新的倍半萜烯，命名为espadalide（1），具有低微摩尔效力，在克隆形成试验中非常有效。另外，从G.下层白。Daleafrutescens分离得到两个新的异戊二烯化查尔酮化合物，分别命名为sanjuanetine（4）和sanjoseetine（5），并从Verbesinavirginica中分离得到已知的倍半萜verbesindiol（6）。机制研究表明，1-4引起G2/M积累和异常有丝分裂纺锤体的形成。微管蛋白聚合测定显示4增加微管蛋白聚合的初始速率，但不改变总微管蛋白聚合物水平，并且1-3对微管蛋白聚合没有影响。尽管具有细胞毒活性，但化合物6并未引发细胞周期分布的变化，并且具有不同于其它化合物的作用机制。这项研究表明，新的化合物具有显着的生物活性密切相关的未得到满足的肿瘤学的需要，可以从得克萨斯州的本地植物。
There remains a critical need for more effective therapies for the treatment of late-stage and metastatic prostate cancers. Three Texas native plants yielded three new and three known compounds with antiproliferative and cytotoxic activities against prostate cancer cells with IC50 values in the range 1.7–35.0 µM. A new sesquiterpene named espadalide (1), isolated from Gochnatia hypoleuca, had low micromolar potency and was highly effective in clonogenic assays. Two known bioactive germacranolides (2 and 3) were additionally isolated from G. hypoleuca. Dalea frutescens yielded two new isoprenylated chalcones, named sanjuanolide (4) and sanjoseolide (5), and the known sesquiterpenediol verbesindiol (6) was isolated from Verbesina virginica. Mechanistic studies showed that 1–4 caused G2/M accumulation and the formation of abnormal mitotic spindles. Tubulin polymerization assays revealed that 4 increased the initial rate of tubulin polymerization, but did not change total tubulin polymer levels, and 1–3 had no effects on tubulin polymerization. Despite its cytotoxic activity, compound 6 did not initiate changes in cell cycle distribution and has a mechanism of action different from the other compounds. This study demonstrates that new compounds with significant biological activities germane to unmet oncological needs can be isolated from Texas native plants.