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New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology
Persefoni Thomopoulou1, Julia Sachs2, Nicole Teusch2
1Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Cologne, Germany.
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).
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