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Thomopoulou P, Sachs J, Teusch N, et al. New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology. ACS Med Chem Lett. 2015;7(2):188-91doi: 10.1021/acsmedchemlett.5b00418.
Thomopoulou, P., Sachs, J., Teusch, N., Mariappan, A., Gopalakrishnan, J., & Schmalz, H. G. (2016). New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology. ACS medicinal chemistry letters, 7(2), 188-91. https://doi.org/10.1021/acsmedchemlett.5b00418
Thomopoulou, Persefoni, et al. "New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology." ACS medicinal chemistry letters vol. 7,2 (2016): 188-91. doi: https://doi.org/10.1021/acsmedchemlett.5b00418
Thomopoulou P, Sachs J, Teusch N, Mariappan A, Gopalakrishnan J, Schmalz HG. 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. eCollection 2016 Feb 11. PMID: 26985296; PMCID: PMC4753549.
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ACS Med Chem Lett. 2015 Dec 29;7(2):188-91. doi: 10.1021/acsmedchemlett.5b00418. eCollection 2016 Feb 11.

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

ACS medicinal chemistry letters

Persefoni Thomopoulou, Julia Sachs, Nicole Teusch, Aruljothi Mariappan, Jay Gopalakrishnan, Hans-Günther Schmalz

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 PMCID: PMC4753549 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

References

  1. Med Biol. 1984;62(6):338-43 - PubMed
  2. J Med Chem. 2014 Dec 26;57(24):10391-403 - PubMed
  3. Br J Cancer. 2015 Sep 1;113(5):693-8 - PubMed
  4. Med Res Rev. 1988 Jan-Mar;8(1):77-94 - PubMed
  5. J Immunol Methods. 1993 Mar 15;160(1):81-8 - PubMed
  6. Science. 2012 Jan 27;335(6067):422-6 - PubMed
  7. ChemMedChem. 2010 May 3;5(5):661-5 - PubMed
  8. Chembiochem. 2013 Aug 19;14(12):1444-9 - PubMed
  9. Cell Death Differ. 2012 Aug;19(8):1255-67 - PubMed
  10. Expert Opin Pharmacother. 2010 Dec;11(17):2933-8 - PubMed
  11. Nat Rev Drug Discov. 2010 Oct;9(10):790-803 - PubMed
  12. J Org Chem. 2004 Dec 24;69(26):8987-96 - PubMed
  13. Chem Rev. 2008 Aug;108(8):2952-3015 - PubMed
  14. Nature. 2009 Jul 9;460(7252):278-82 - PubMed
  15. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3776-80 - PubMed
  16. Bioorg Khim. 2013 Sep-Oct;39(5):609-18 - PubMed
  17. Drug Discov Today Dis Mech. 2013 Dec 1;10(3-4):e119-e124 - PubMed
  18. Med Oncol. 2015 Jul;32(7):205 - PubMed
  19. Clin Toxicol (Phila). 2010 Jun;48(5):407-14 - PubMed
  20. Chem Biol Drug Des. 2011 Dec;78(6):913-22 - PubMed
  21. J Med Chem. 2012 Dec 27;55(24):11062-6 - PubMed
  22. Nature. 2014 Jun 5;510(7503):167-71 - PubMed
  23. Recent Pat Anticancer Drug Discov. 2014 May;9(2):176-220 - PubMed
  24. Bioorg Med Chem. 2011 Sep 15;19(18):5529-38 - PubMed
  25. Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9 - PubMed
  26. Future Med Chem. 2013 Mar;5(3):339-52 - PubMed
  27. Cell Death Dis. 2014 Nov 20;5:e1538 - PubMed
  28. Exp Mol Med. 2013 Apr 19;45:e19 - PubMed

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