2. Academic Validation
  3. Synthesis of thiocolchicine amine derivatives and evaluation of their antiproliferative activity

Synthesis of thiocolchicine amine derivatives and evaluation of their antiproliferative activity

  • Bioorg Med Chem Lett. 2021 Nov 15:52:128382. doi: 10.1016/j.bmcl.2021.128382.
Dominika Czerwonka 1,  Ewa Maj 2,  Joanna Wietrzyk 2,  Adam Huczyński 3
Affiliations

Affiliations

  • 1 Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznan, Poland.
  • 2 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
  • 3 Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznan, Poland. Electronic address: adhucz@amu.edu.pl.
PMID: 34592435 DOI: 10.1016/j.bmcl.2021.128382
Abstract

A series of 22 amine analogs of thiocolchicine were synthesized using the reductive amination reaction. The antiproliferative activities of these compounds were tested against four tumor cell lines as well as one normal cell line. The tested analogs exhibited IC50 values in the nanomolar range accompanied by high selectivity indexes, and most importantly, they were able to break the drug resistance of the human colon adenocarcinoma resistant cell line (LoVo/DX). Also, a correlation between the antiproliferative activity and physicochemical properties of the novel compounds has been found.

Keywords

Antiproliferative activity; Colchicine analogs; Natural products; Reductive amination; Structure–activity relationship; Thiocolchicine.

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