2. Academic Validation
  3. New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology

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

  • ACS Med Chem Lett. 2015 Dec 29;7(2):188-91. doi: 10.1021/acsmedchemlett.5b00418.
Persefoni Thomopoulou 1,  Julia Sachs 2,  Nicole Teusch 2,  Aruljothi Mariappan 3,  Jay Gopalakrishnan 3,  Hans-Günther Schmalz 1
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Cologne, Germany.
  • 2 Technische Hochschule Koeln, Kaiser-Wilhelm-Allee , Building E39, 51373 Leverkusen, Germany.
  • 3 Center for Molecular Medicine and Institute of Biochemistry II of the University of Cologne , Robert-Koch-Str. 21, 50931 Cologne, Germany.
PMID: 26985296 DOI: 10.1021/acsmedchemlett.5b00418
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).

Keywords

Colchicine; antitumoral compounds; click chemistry; resistance; tubulin.

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