法國國家科研中心的研究人員日前通過實(shí)驗(yàn)發(fā)現(xiàn)，“玫瑰樹堿”的衍生物對(duì)多種癌癥具有特別療效,，這一發(fā)現(xiàn)將有助于抗癌新藥的研發(fā),。
該研究由法國國家科研中心與法國原子能委員會(huì)、法國國家健康與醫(yī)學(xué)研究所和居里大學(xué)等機(jī)構(gòu)聯(lián)合完成,。研究人員在最新一期美國《癌癥研究》上報(bào)告說,，“玫瑰樹堿”可從大洋洲一種常見玫瑰植株的葉子中提取，它通過破壞脫氧核糖核酸殺死癌細(xì)胞,，功效顯著,。但與此同時(shí)，它攻擊的目標(biāo)性較差,，會(huì)“誤殺”不少健康細(xì)胞,，從而帶來嚴(yán)重的副作用。
報(bào)告說，研究人員通過大量篩選,，找到了“玫瑰樹堿”的幾種衍生物,，這些衍生物對(duì)蛋白激酶CK2具有特別的功效。蛋白激酶在乳腺癌和前列腺癌等多種癌癥的擴(kuò)散中起著關(guān)鍵作用,，如能抑制它的活性,，治療癌癥事半功倍。研究人員隨后在試管內(nèi)和實(shí)驗(yàn)鼠身上進(jìn)行了測試,，都取得成功,。
研究小組負(fù)責(zé)人克洛德·科歇表示，“玫瑰樹堿”的這些衍生物能有效抑制腫瘤擴(kuò)散,，同時(shí)它們的目標(biāo)性很強(qiáng),，產(chǎn)生的副作用比較小。這項(xiàng)研究成果將為癌癥治療開辟新途徑,。（生物谷Bioon.com）
生物谷推薦原文出處：
Cancer Research doi: 10.1158/0008-5472.CAN-10-0917
Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
Renaud Prudent1,2,3, Virginie Moucadel1,2,3, Chi-Hung Nguyen4, Caroline Barette5, Frédéric Schmidt6,7, Jean-Claude Florent6,7, Laurence Lafanechère5, Céline F Sautel1,2,3, Eve Duchemin-Pelletier1,2,3, Elodie Spreux1,2,3, Odile Filhol1,2,3, Jean-Baptiste Reiser8, and Claude Cochet1,2,3
Abstract
The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2–inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters.
