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Open AccessArticle

Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

1
Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61–614 Poznań, Poland
2
TriMen Chemicals, Piłsudskiego 141, 92–318 Łódź, Poland
3
Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada
4
Institute of Low Temperature and Structure Research, Polish Academy of Sciences, PO Box 1410, 50–950 Wrocław, Poland
5
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53–114 Wrocław, Poland
6
DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Qiao-Hong Chen
Molecules 2020, 25(8), 1789; https://doi.org/10.3390/molecules25081789
Received: 16 March 2020 / Revised: 5 April 2020 / Accepted: 11 April 2020 / Published: 14 April 2020
(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation)
Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin. View Full-Text
Keywords: anticancer agents; colchicine amide; colchicine sulfonamide; tubulin inhibitors; docking studies; crystal structure anticancer agents; colchicine amide; colchicine sulfonamide; tubulin inhibitors; docking studies; crystal structure
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MDPI and ACS Style

Krzywik, J.; Mozga, W.; Aminpour, M.; Janczak, J.; Maj, E.; Wietrzyk, J.; Tuszyński, J.A.; Huczyński, A. Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents. Molecules 2020, 25, 1789.

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