New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology

详细信息    查看全文

• 作者：Persefoni Thomopoulou ; Julia Sachs ; Nicole Teusch ; Aruljothi Mariappan ; Jay Gopalakrishnan ; Hans-Günther Schmalz
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：February 11, 2016
• 年：2016
• 卷：7
• 期：2
• 页码：188-191
• 全文大小：322K
• ISSN：1948-5875

文摘

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).