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A series of [1,2,3]triazolo[4,5- d ]pyrimidine derivatives bearing a hydrazone moiety were designed, synthesized and evaluated for their antiproliferative activity against several cancer cell lines of different origins by MTT assay. Most of the synthesized compounds demonstrated moderate to good activity against the cancer cell lines selected. Especially, compound 43 showed the most potent antiproliferative activity as well as good selectivity between cancer and normal cells (IC 50 values of 0.85 μM against MGC-803 and 56.17 μM against GES-1). In addition, compound 43 evidently inhibited the colony formation of MGC-803 cells at 0.8 μM. Further mechanism studies revealed that compound 43 could induce apoptosis of MGC-803 cells probably through the mitochondrial pathway accompanied with decrease of the mitochondrial membrane potential (MMP), activations of caspase-9/3, up-regulation of the expression of Bax, Bak and PUMA, as well as down-regulation of that of Bcl-2 and Mcl-1. [ABSTRACT FROM AUTHOR]

A series of new isatin/triazole conjugates were designed based on the hypothesis that the ester-linked compounds could be enzymatically hydrolyzed by cellular esterases inside the cells. These compounds showed moderate to good growth inhibition toward the tested cancer cells, exerted selective inhibition toward MGC-803 cells and were less toxic to normal cells HL-7702 and GES-1. Of these compounds, compound 5a showed the best inhibitory activity against MGC-803 cells (IC 50 = 9.78 μM), induced apoptosis through multiple mechanisms, as well as inhibited migration of MGC-803 cells. [ABSTRACT FROM AUTHOR]