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Paper | Regular issue | Vol 92, No. 4, 2016, pp.688-699
Published online, 12th February, 2016
DOI: 10.3987/COM-16-13419
■ Application of Mannich and Michael Reactions in Synthesis of Pyridopyrimido[2,1-b][1,3,5]thiadiazinones and Pyridopyrimido[2,1-b][1,3]thiazinones as Anticancer Agents

Sobhi M. Gomha,* Magda A. Abdallah, Mahmoud A. Mourad, and Mahmoud M. Elaasser

*Department of Organic Chemistry, Cairo University, Giza-Haram 12613, Egypt

Abstract

A new series of pyrido[2',3':4,5]pyrimido[2,1-b][1,3,5]thiadiazinones were prepared by aminomethylation of pyridopyrimidinethione with a variety of primary aromatic amines and formaldehyde solution (37%) through Mannich reaction. Also, another series of pyrido[2',3:4,5]pyrimido[2,1-b][1,3]thiazinones were synthesized by Micheal addition reaction of pyridopyrimidinethione to the activated double bond of a number of arylidene malononitrile and ethyl 3-aryl-2-cyanopropenoate. The mechanism of formation of the synthesized compounds was discussed and the assigned structure was established via microanalysis and spectral data (IR, 1HNMR and Mass). In addition, the antitumor activities of the synthesized compounds were investigated in comparison with the well-known anticancer standard drugs doxorubcin and Imatinib using MTT assay. The results revealed that the tested compounds showed high variation in the inhibitory growth rates and activities against the tested tumor cell lines in a concentration dependent manner. The highest activity was measured for compound 4g against human hepatocellular carcinoma (HepG2) cells and compound 4i in case of breast carcinoma (MCF-7) cells compared with reference drug imatinib. These results revealed that these compounds exhibited promising antitumor activities.