| PI3K/mTOR抑制剂的合成及生物活性 |
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| 引用本文： | 王磊,郑国钧,季奇,陈博,巩龙龙,高聪敏,杜镇建,张兴民.PI3K/mTOR抑制剂的合成及生物活性[J].高等学校化学学报,2017,38(9). |
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| 作者姓名： | 王磊 郑国钧 季奇 陈博 巩龙龙 高聪敏 杜镇建 张兴民 |
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| 作者单位： | 1. 北京化工大学生命科学与技术学院,北京100029;北京富龙康泰生物技术有限公司,北京101111;2. 北京化工大学生命科学与技术学院,北京,100029;3. 北京富龙康泰生物技术有限公司,北京,101111 |
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| 基金项目： | 北京市科委生物医药创新品种研发项目，北京市经济技术开发区科技创新专项项目(批准号:JSYF2013138)资助.
Supported by the Research and Development Project of Beijing Municipal Commission of Science and Technology |
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| 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.
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| 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 |
Synthesis and Biological Activity of Novel PI3K/mTOR Inhibitors |
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| WANG Lei,ZHENG Guojun,JI Qi,CHEN Bo,GONG Longlong,GAO Congmin,DU Zhenjian,ZHANG Xingmin.Synthesis and Biological Activity of Novel PI3K/mTOR Inhibitors[J].Chemical Research In Chinese Universities,2017,38(9). |
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| Authors: | WANG Lei ZHENG Guojun JI Qi CHEN Bo GONG Longlong GAO Congmin DU Zhenjian ZHANG Xingmin |
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| Abstract: | 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. |
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| Keywords: | Phosphatidylinositol 3-kinase/mammalian target of rapamycin( PI3K/mTOR) inhibitor Antitumor viability Structure-activity relationship |
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