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).
