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.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
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~~
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
Phosphatidylinositol 3-kinase/mammalian target of rapamycin(PI3K/mTOR) inhibitor
Antitumor viability
Structure-activity relationship