Pyrimidooxadiazine and triazolopyrimidooxadiazine derivatives: Synthesis and cytotoxic evaluation in human cancer cell lines

Abstract

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.

Synthesis and evaluation of cytotoxicity of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles

“…Nuclear morphology of MCF 7 cells was analyzed with DAPI (4' 6 diamidino 2 phe nylindole) staining [35]. MCF 7 cells were seeded on to glass cover slips in a six well plate.…”

Synthesis and Antiproliferative Evaluation of New Pyrimido[1,6‐a]Thieno[2,3‐d]Pyrimidine Derivatives

“…Based on the importance of these compounds and further to our ongoing research on the synthesis of fused pyrimidines as biologically important molecules , we commenced our synthetic strategy towards a series of novel pyrimido[1,6‐ a ]thieno[2,3‐ d ]pyrimidines and screened them for antiproliferative activity against breast cancer cell line (MCF‐7), which is known as a widely used model system for the study of breast cancer .…”

Synthesis, Characterisation, and in Vitro Antibacterial Evaluation of a New Class of 2-substituted-4-methyl-7,8-dihydro-5H-pyrimido[4,5-d]thiazolo[3,2-a] Pyrimidines

“…the related pyrimido [4,5-d]pyrimidine derivatives after the elimination of dimethylamine from the cycloadducts as well as the oxidative aromatisation. 17 In view of these observations and in continuation of our study on fused pyrimidines, [18][19][20][21] we have undertaken the synthesis of some new derivatives of pyrimido [4,5-d]thiazolo [3,2-a] pyrimidine and tested their antibacterial activity.…”