新型秋水仙碱衍生的三唑类化合物及其对细胞毒性和微管形态的影响。
New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology.
作者信息
Thomopoulou Persefoni, Sachs Julia, Teusch Nicole, Mariappan Aruljothi, Gopalakrishnan Jay, Schmalz Hans-Günther
机构信息
Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Cologne, Germany.
Technische Hochschule Koeln, Kaiser-Wilhelm-Allee , Building E39, 51373 Leverkusen, Germany.
出版信息
ACS Med Chem Lett. 2015 Dec 29;7(2):188-91. doi: 10.1021/acsmedchemlett.5b00418. eCollection 2016 Feb 11.
Abstract
A series of new colchicinoids with a variable triazole unit at C-7 was synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (click-chemistry) of a colchicine-derived azide with various alkynes and the cytotoxicity against THP-1 and Jurkat cancer cell lines was used for structural optimization. Three particularly active compounds (IC50 ≤ 5 nM) were additionally investigated with respect to their efficacy against relevant solid tumor cell lines (HeLa, A549, and SK MES 1). Besides distorting the microtubule morphology by tubulin depolymerization, one compound also exhibited a pronounced centrosome declustering effect in triple negative breast cancer cells (MDA-MB-231) and nonsmall cell lung cancer cells (H1975).
摘要
通过秋水仙碱衍生的叠氮化物与各种炔烃的铜（I）催化的1,3-偶极环加成反应（点击化学）合成了一系列在C-7位具有可变三唑单元的新型秋水仙碱类似物，并将其对THP-1和Jurkat癌细胞系的细胞毒性用于结构优化。另外，针对三种特别活跃的化合物（IC50≤5 nM）对相关实体瘤细胞系（HeLa、A549和SK MES 1）的疗效进行了研究。除了通过微管蛋白解聚使微管形态畸变外，一种化合物在三阴性乳腺癌细胞（MDA-MB-231）和非小细胞肺癌细胞（H1975）中还表现出明显的中心体去簇集效应。
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