Synthesis and anticancer evaluation of some novel pyrimido[5,4-e][1,2,4]triazines and pyrazolo[3,4-d]pyrimidine using DMF-DMA as methylating and cyclizing agent

Samar A El-Kalyoubi

doi:10.1186/s13065-018-0424-3

Synthesis and anticancer evaluation of some novel pyrimido[5,4-e][1,2,4]triazines and pyrazolo[3,4-d]pyrimidine using DMF-DMA as methylating and cyclizing agent

Chem Cent J. 2018 May 23;12(1):64. doi: 10.1186/s13065-018-0424-3.

Author

Samar A El-Kalyoubi^{1

2}

Affiliations

¹ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, 11651, Egypt. s.elkalyoubi@hotmail.com.
² Department of Medical Chemistry, Faculty of Applied Medical Sciences (Female Section), Jazan University, Jazan, 45142, Saudi Arabia. s.elkalyoubi@hotmail.com.

Abstract

Background: Described a series of main target compounds pyrimido[5,4-e][1,2,4]triazines is obtained via condensation of 6-hydrazinyluracil with different aromatic aldehydes to give the hydrazones followed by nitrosation with HNO₂ then intramolecular cyclization. On the other hand, pyrazolopyrimidines can be obtained by the reaction of hydrazones with dimethylformamide-dimethylacetal (DMF-DMA), DMF-DMA in the presence of DMF or by refluxing the hydrazinyluracil with DMF-DMA in the presence of DMF directly. The newly synthesized compounds are evaluated in vitro for their anticancer activity against human lung carcinoma (A549).

Results: A newly substituted compounds of benzaldehyde-pyrimidin-4-yl)hydrazones (5a-f), pyrimido[5,4-e][1,2,4]triazines 6a-e, arylethylidenehydrazinylpyrimidine 7a,b and pyrazolopyrimidines 9,11 are screened for cytotoxic activity against human lung carcinoma (A549) cell line. They exhibited a good yield. Compound 6b shows the highest effect with IC₅₀ value 3.6 μM, followed by compounds 9, 5a, 8, 5e, 6e, 5b, 5f, 7a, 5c, 6c, 7b, 6a, 11, 5d and 6d.

Conclusion: A simple and efficient route is used for the synthesis of pyrimido[5,4-e][1,2,4]triazines and pyrazolopyrimidines. The synthesized compounds are screened for antitumor activity.

Keywords: 6-Hydrazinyluracil; Anticancer activities; Dimethylformamide-dimethylacetal; Pyrazolopyrimidine; Pyrimidotriazine.