新型TTK抑制剂N-10的合成及对三阴性乳腺癌细胞的影响  

Synthesis of Novel TTK Inhibitors N-10 and effects on Triple-negative Breast Cancer Cells

作　　者：李楠[1,2] 刘巍 Li Nan;Liu Wei(School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Tianjin Institute of Pharmaceutical Research,Tianjin 300450,China)

机构地区：[1]天津医科大学药学院,天津300070 [2]天津药物研究院有限公司,天津300450

出　　处：《广东化工》2024年第8期119-121,118,共4页Guangdong Chemical Industry

摘　　要：本研究通过化学方法合成一种新型TTK抑制剂N-10,并探究其对TTK激酶的抑制作用,以及对三阴性乳腺癌细胞增殖、集落生成、迁移和侵袭的影响。以4-溴-3-羟基苯甲酸甲酯为原料,通过烷基化、水解、缩合和suzuki偶联反应合成目标化合物N-10;利用酶学实验,检测N-10对TTK激酶的抑制作用;通过CellTiter-Glo实验检测N-10对三阴性乳腺癌细胞增殖的抑制作用;通过进行细胞划痕实验和Transwell侵袭实验,深入研究了N-10对三阴性乳腺癌细胞在迁移和侵袭能力方面的影响。实验结果显示,N-10对TTK激酶具有显著的活性抑制作用,并能够有效抑制三阴性乳腺癌细胞MDA-MB-231的生长增殖。减弱三阴性乳腺癌细胞MDA-MB-231的迁移和侵袭能力,为TTK抑制剂N-10的深入研究提供了科学依据。In this study,a novel TTK inhibitor N-10 was synthesized by chemical methods,and its inhibitory effect on TTK kinase,as well as its effect on the proliferation,colony formation,migration and invasion of triple-negative breast cancer cells was investigated.The target compound N-10 was synthesized from methyl 4-bromo-3-hydroxybenzoate by alkylation,hydrolysis,condensation and suzuki coupling reaction.The inhibitory effect of N-10 on TTK kinase was detected by enzyme experiments.The inhibitory effect of N-10 on the proliferation of triple negative breast cancer cells was detected by CellTiter-Glo assay.The effects of N-10 on migration and invasion ability of triple negative breast cancer cells were studied by cell scratch and Transwell invasion experiments.The experimental results showed that N-10 had a significant inhibitory effect on TTK kinase activity,and could effectively inhibit the growth and proliferation of triple negative breast cancer cells MDA-MB-231.The migration and invasion ability of triple negative breast cancer cells MDA-MB-231 was weakened,which provided scientific basis for further study of TTK inhibitor N-10.

关 键 词：药物合成 三阴性乳腺癌 纺锤体装配检验点 TTK抑制剂 

分 类 号：R965[医药卫生—药理学]