title: New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology.
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).
authors.affiliation: Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Cologne, Germany.
authors.forename: Persefoni
authors.initials: P
authors.lastname: Thomopoulou
authors.affiliation: Technische Hochschule Koeln, Kaiser-Wilhelm-Allee , Building E39, 51373 Leverkusen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Sachs
authors.affiliation: Technische Hochschule Koeln, Kaiser-Wilhelm-Allee , Building E39, 51373 Leverkusen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Teusch
authors.affiliation: Center for Molecular Medicine and Institute of Biochemistry II of the University of Cologne , Robert-Koch-Str. 21, 50931 Cologne, Germany.
authors.forename: Aruljothi
authors.initials: A
authors.lastname: Mariappan
authors.affiliation: Center for Molecular Medicine and Institute of Biochemistry II of the University of Cologne , Robert-Koch-Str. 21, 50931 Cologne, Germany.
authors.forename: Jay
authors.initials: J
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Cologne, Germany.
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Schmalz
keywords: Colchicine; antitumoral compounds; click chemistry; resistance; tubulin