In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.