New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking

Krzywik, Julia; Aminpour, Maral; Maj, Ewa; Mozga, Witold; Wietrzyk, Joanna; Tuszyński, Jack A.; Huczyński, Adam

doi:10.3390/molecules25153540

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New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking

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Adam Huczyński

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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

Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada

⁴

Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland

⁵

DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy

Author to whom correspondence should be addressed.

Academic Editors: Bartosz Tylkowski, Anna Bajek and Krzysztof Roszkowski

Molecules 2020, 25(15), 3540; https://doi.org/10.3390/molecules25153540

Received: 14 July 2020 / Revised: 28 July 2020 / Accepted: 31 July 2020 / Published: 2 August 2020

(This article belongs to the Special Issue Anticancer Drug Discovery and Development)

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Abstract

Colchicine is a well-known anticancer compound showing antimitotic effect on cells. Its high cytotoxic activity against different cancer cell lines has been demonstrated many times. In this paper we report the syntheses and spectroscopic analyses of novel colchicine derivatives obtained by structural modifications at C7 (carbon-nitrogen single bond) and C10 (methylamino group) positions. All the obtained compounds have been tested in vitro to determine their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX, and BALB/3T3 cell lines. The majority of obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin and cisplatin against the tested cancerous cell lines. Additionally, most of the presented derivatives were able to overcome the resistance of LoVo/DX cells. Additionally, their mode of binding to β-tubulin was evaluated in silico. Molecular docking studies showed that apart from the initial amides 1 and 2, compound 14, which had the best antiproliferative activity (IC₅₀ = 0.1–1.6 nM), stood out also in terms of its predicted binding energy and probably binds best into the active site of βI-tubulin isotype. View Full-Text

Keywords: anticancer agents; colchicine derivatives; reductive alkylation; tubulin inhibitors; docking studies

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MDPI and ACS Style

Krzywik, J.; Aminpour, M.; Maj, E.; Mozga, W.; Wietrzyk, J.; Tuszyński, J.A.; Huczyński, A. New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking. Molecules 2020, 25, 3540. https://doi.org/10.3390/molecules25153540

AMA Style

Krzywik J, Aminpour M, Maj E, Mozga W, Wietrzyk J, Tuszyński JA, Huczyński A. New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking. Molecules. 2020; 25(15):3540. https://doi.org/10.3390/molecules25153540

Chicago/Turabian Style

Krzywik, Julia, Maral Aminpour, Ewa Maj, Witold Mozga, Joanna Wietrzyk, Jack A. Tuszyński, and Adam Huczyński. 2020. "New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking" Molecules 25, no. 15: 3540. https://doi.org/10.3390/molecules25153540

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New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking

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