Abstract
In this study, five derivatives of triazepino[2,3-a] quinazoline-2,7(1H)-dione were synthesized and their anticancer activities were investigated both in two-dimensional-monolayer and three-dimensional-multicellular spheroids cancer models. All the five compounds showed very high anticancer activities against the 11 cancer cell types that have been investigated in the monolayer model. Comparing the results of both monolayer and multicellular spheroids models of the anticancer activity of these five compounds, we can conclude that the meta-methyl derivative induced its anticancer activity through apoptosis to give the best results in the monolayer model. However, in the multicellular spheroids model its apoptotic activity induced moderate anticancer activity (64 % cytotoxicity). On the other hand, both two nitro-derivatives either in meta-position or para-position, did not show potent pro-apoptotic activities toward the monolayer model but showed very high cytotoxic activity toward the multicellular spheroids model (100 %). These results reveal that the cell death mechanism induced by both nitro-compounds is exerted via other path than the apoptosis. Interestingly, all the tested compounds were generally safe to normal cells spheroids when tested at the same concentration.
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Acknowledgments
The authors are very grateful for professor Stig Linder in Oncology Department, Karolinska Institute, Sweden, for generously allowing the experiments of spheroids testing and apoptosis assessment to be performed at his laboratory, using his laboratory facilities and supplies. This publication has been produced with partial financial assistance of the European Union under the ENPI CBC Mediterranean Sea Basin Programme. The contents of this document is the sole responsibility of National Research Center and can under no circumstances be regarded as reflecting the position of the European Union or of the Programme’s management structures.
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Awad, H.M., Fayad, W., El-Hallouty, S.M. et al. Anticancer activity of some [1,2,4]triazepino[2,3-a] quinazoline derivatives: monolayer and multicellular spheroids in vitro models. Med Chem Res 25, 1952–1957 (2016). https://doi.org/10.1007/s00044-016-1639-2
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DOI: https://doi.org/10.1007/s00044-016-1639-2