Abstract
Dual action alkyl(aryl)amino-1,3,5-triazines functionalized with nitrogen mustards were obtained by treating 2-alkyl(aryl) amino-4-chloro-6-methoxy-1,3,5-triazines with amines or amino acid methyl esters, followed by reactions with 1,4-diazabicyclo[2.2.2]octane (DABCO) and rearrangement with an opening diazabicyclic fragment, leading to the formation of 2-chloroethylamino moiety. In vitro antitumor activity was tested in the standard human breast cancer MCF-7 and MDA-MB-231cell lines using flow cytometry, based on the detection of apoptosis through qualitative analysis of morphological changes, DNA fragmentation, DNA loss and membrane changes. For all the compounds studied, induced apoptosis was substantially stronger than necrosis at concentrations of both 5 μM and 50 μM, and in some cases there was no increase in necrotic cell death for the estrogen dependent MCF-7 cell line. The most active compounds were derivatives of triazine substituted with phenylamine (IC50 = 12.30 μM) and/or p-tolylamine fragments (IC50 = 7.40 μM).
Keywords: Hybrid drugs, apoptosis inducers, cytotoxicity, alkylating agent, melamine, triazine.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis of Arylamino-1,3,5-triazines Functionalized with Alkylatin 2-chloroethylamine Fragments and Studies of their Cytotoxicity on the Breast Cancer MCF-7 Cell Line
Volume: 16 Issue: 11
Author(s): Justyna Fraczyk, Beata Kolesinska, Monika Swiontek, Wojciech Lipinski, Danuta Drozdowska and Zbigniew Jerzy Kaminski
Affiliation:
Keywords: Hybrid drugs, apoptosis inducers, cytotoxicity, alkylating agent, melamine, triazine.
Abstract: Dual action alkyl(aryl)amino-1,3,5-triazines functionalized with nitrogen mustards were obtained by treating 2-alkyl(aryl) amino-4-chloro-6-methoxy-1,3,5-triazines with amines or amino acid methyl esters, followed by reactions with 1,4-diazabicyclo[2.2.2]octane (DABCO) and rearrangement with an opening diazabicyclic fragment, leading to the formation of 2-chloroethylamino moiety. In vitro antitumor activity was tested in the standard human breast cancer MCF-7 and MDA-MB-231cell lines using flow cytometry, based on the detection of apoptosis through qualitative analysis of morphological changes, DNA fragmentation, DNA loss and membrane changes. For all the compounds studied, induced apoptosis was substantially stronger than necrosis at concentrations of both 5 μM and 50 μM, and in some cases there was no increase in necrotic cell death for the estrogen dependent MCF-7 cell line. The most active compounds were derivatives of triazine substituted with phenylamine (IC50 = 12.30 μM) and/or p-tolylamine fragments (IC50 = 7.40 μM).
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Fraczyk Justyna, Kolesinska Beata, Swiontek Monika, Lipinski Wojciech, Drozdowska Danuta and Kaminski Jerzy Zbigniew, Synthesis of Arylamino-1,3,5-triazines Functionalized with Alkylatin 2-chloroethylamine Fragments and Studies of their Cytotoxicity on the Breast Cancer MCF-7 Cell Line, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (11) . https://dx.doi.org/10.2174/1871520616666160204111430
DOI https://dx.doi.org/10.2174/1871520616666160204111430 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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