2. Academic Validation
  3. Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties

Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties

  • Bioorg Med Chem Lett. 2021 Sep 1:47:128197. doi: 10.1016/j.bmcl.2021.128197.
Julia Krzywik 1,  Ewa Maj 2,  Anna Nasulewicz-Goldeman 2,  Witold Mozga 3,  Joanna Wietrzyk 2,  Adam Huczyński 4
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 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
  • 3 TriMen Chemicals, Piłsudskiego 141, 92-318 Łódź, Poland.
  • 4 Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland. Electronic address: adhucz@amu.edu.pl.
PMID: 34116158 DOI: 10.1016/j.bmcl.2021.128197
Abstract

A new series of 10-demethoxy-10-methylaminocolchicines bearing urea, thiourea or aguanidine moieties at position C7 has been designed, synthesized and evaluated for in vitro Anticancer activity against different Cancer cell lines (A549, MCF-7, LoVo, LoVo/DX). The majority of the new derivatives were active in the nanomolar range and were characterized by lower IC50 values than cisplatin or doxorubicin. Two ureas (4 and 8) and thioureas (19 and 25) were found to be good antiproliferative agents (low IC50 values and high SI) and could prove to be promising candidates for further research in the field of Anticancer drugs based on the colchicine skeleton.

Keywords

Anticancer agents; Antiproliferative activity; Colchicine derivatives.

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