首页|新型TTK抑制剂N-10的合成及对三阴性乳腺癌细胞的影响

新型TTK抑制剂N-10的合成及对三阴性乳腺癌细胞的影响

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

drug synthesistriple negative breast cancerspindle assembly inspection pointTTK inhibitor

李楠、刘巍

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天津医科大学药学院,天津 300070

天津药物研究院有限公司,天津 300450

药物合成 三阴性乳腺癌 纺锤体装配检验点 TTK抑制剂

2024

广东化工
广东省石油化工研究院

广东化工

影响因子:0.288
ISSN:1007-1865
年,卷(期):2024.51(8)