Abstract
Continuing our research in the field of new heterocyclic compounds, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3′,2′:4,5](furo)thieno[3,2-d]pyrimidines as well as of two new heterocyclic systems: furo[2–e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine. Thus, by refluxing the 8-chloro derivatives of pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidines with various amines, the relevant pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidin-8-amines were obtained. Further, the cyclization of some amines under the action of phosphorus oxychloride led to the formation of new heterorings: imidazo[1,2-c]pyrimidine and pyrimido[1,2-c]pyrimidine. The possible antitumor activity of the newly synthesized compounds was evaluated in vitro. The biological tests evidenced that some of them showed pronounced antitumor activity. A study of the structure–activity relationships revealed that the compound activity depended mostly on the nature of the amine fragments. A docking analysis was also performed for the most active compounds.
Highlights
Enzymatic DNA methylation by DNA methyltransferases is an important constituent of the cell epigenetic regulatory system that modulates gene expression without altering the DNA base sequence
We have previously reported on the synthesis and biological activity of some amino derivatives of condensed furo- and thieno [3,2-d]pyrimidines [12,13,14,15,16]
Continuing our studies in the field of searching for new heterocyclic compounds of biological interest, we report on the synthesis and antitumor activity of new amino derivatives of pyrido[30,20 :4,5](furo)thieno[3,2-d]pyrimidines as well as new heterocyclic systems: furo[2,3-e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine
Summary
Enzymatic DNA methylation by DNA methyltransferases is an important constituent of the cell epigenetic regulatory system that modulates gene expression without altering the DNA base sequence. It is tissue- (cell) and age-specific and is involved in the regulation of all genetic functions, Molecules 2019, 24, 3952; doi:10.3390/molecules24213952 www.mdpi.com/journal/molecules. The methylation pattern of DNA is inherited, and significant distortions result in defects in growth and development. There is no doubt that some changes in DNA methylation induce cancer, premature aging, apoptosis, and death [1]. Malignant cells have a different DNA methylation pattern and a different set of expressed DNA methyltransferase activities compared to normal cells [2].
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