PI3K/mTOR抑制剂的合成及生物活性  

Synthesis and Biological Activity of Novel PI3K/mTOR Inhibitors

作　　者：王磊[1,2] 郑国钧 季奇[2] 陈博 巩龙龙 高聪敏 杜镇建 张兴民 

机构地区：[1]北京化工大学生命科学与技术学院,北京100029 [2]北京富龙康泰生物技术有限公司,北京101111

出　　处：《高等学校化学学报》2017年第9期1590-1595,共6页Chemical Journal of Chinese Universities

基　　金：北京市科委生物医药创新品种研发项目(批准号:Z161100000116018);北京市经济技术开发区科技创新专项项目(批准号:JSYF2013138)资助~~

摘　　要：以NVP-BEZ235为先导化合物,设计合成了10个磷脂酰肌醇3-激酶/哺乳动物雷帕霉素靶蛋白(PI3K/mTOR)抑制剂;目标化合物的结构经核磁共振波谱(NMR)和液相色谱-质谱(LC-MS)分析确证.采用噻唑蓝(MTT)比色法在人急性单核细胞白血病细胞株(MV4-11)、人乳腺癌细胞株(BT474)和人前列腺癌细胞株(PC-3)中测定了目标化合物的抗肿瘤活性,并对其构效关系进行了初步的讨论.结果表明,化合物11(FP-189)对MV4-11细胞株表现出较强的抑制活性(IC_(50)=22.5 nmol/L),且具有良好的溶解性,可以作为白血病治疗的候选药物进行下一步开发.A series of new phosphatidylinositol 3-kinase/mammalian target of rapamycin（ PI3K/mTOR）inhibitors with optimized synthetic process was designed and synthesized,the correctness of the structure was determined by ~1 H NMR and LC-MS and the antitumor activities of these compounds were evaluated in 3 tumor celllines by MTT colorimetric method. Compound 11 showed very strong inhibition of MV4-11 cell growth,and was selected as a leading compound for further development of anti-leukemia drug candidate.

关 键 词：磷脂酰肌醇3-激酶/哺乳动物雷帕霉素靶蛋白抑制剂 抗肿瘤活性 构效关系 

分 类 号：O626.32[理学—有机化学]