2. Academic Validation
  3. An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine

An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine

  • Eur J Med Chem. 2021 Apr 5:215:113282. doi: 10.1016/j.ejmech.2021.113282.
Julia Krzywik 1,  Maral Aminpour 2,  Jan Janczak 3,  Ewa Maj 4,  Mahshad Moshari 5,  Witold Mozga 6,  Joanna Wietrzyk 4,  Jack A Tuszyński 7,  Adam Huczyński 8
Affiliations

Affiliations

  • 1 Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614, Poznań, Poland; TriMen Chemicals, Piłsudskiego 141, 92-318, Łódź, Poland.
  • 2 Department of Oncology, University of Alberta, Edmonton, T6G 1Z2, Canada.
  • 3 Institute of Low Temperature and Structure Research, Polish Academy of Sciences, PO Box 1410, 50-950, Wrocław, Poland.
  • 4 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.
  • 5 Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.
  • 6 TriMen Chemicals, Piłsudskiego 141, 92-318, Łódź, Poland.
  • 7 Department of Oncology, University of Alberta, Edmonton, T6G 1Z2, Canada; DIMEAS, Politecnico di Torino, Corso Duca Degli Abruzzi, 24, Torino, 10129, Italy.
  • 8 Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614, Poznań, Poland. Electronic address: adhucz@amu.edu.pl.
PMID: 33611191 DOI: 10.1016/j.ejmech.2021.113282
Abstract

Colchicine shows very high antimitotic activity, therefore, it is used as a lead compound for generation of new Anticancer agents. In the hope of developing novel, useful drugs with more favourable pharmacological profiles, a series of doubly modified colchicine derivatives has been designed, synthesized and characterized. These novel carbamate or thiocarbamate derivatives of 10-demethoxy-10-methylaminocolchicine have been tested for their antiproliferative activity against four human Cancer cell lines. Additionally, their mode of action has been evaluated as colchicine binding site inhibitors, using molecular docking studies. Most of the tested compounds showed greater cytotoxicity (IC50 in a low nanomolar range) and were characterized by a higher selectivity index than standard chemotherapeutics such as cisplatin and doxorubicin as well as unmodified colchicine. Their pharmacological use in Cancer therapy could possibly be accomplished with lower dosages and result in less acute toxicity problems than in the case of colchicine. In addition, we present a QSAR model for predicting the antiproliferative activity of doubly modified derivatives for two tumour cell lines.

Keywords

Anticancer agents; Carbamate; Crystal structure; Docking studies; QSAR; Thiocarbamate; Tubulin inhibitors.

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