Anticancer activity of some [1,2,4]triazepino[2,3-a] quinazoline derivatives: monolayer and multicellular spheroids in vitro models

作者：Awad Hanem M^*; Fayad Walid; El Hallouty Salwa M; Farghaly Thoraya A; Abdallah Mohamad M

来源：Medicinal Chemistry Research, 2016, 25(9): 1952-1957.

DOI：10.1007/s00044-016-1639-2

• [1,2,4]Triazepino[2,3-a] quinazolines
• Anticancer activity
• Apoptosis

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.

• 出版日期2016-9