Synthesis, Antitumor Activity, and Docking Analysis of New Pyrido[3′,2′:4,5]furo(thieno)[3,2-<i>d</i>]pyrimidin-8-amines
Samvel N. Sirakanyan,
Domenico Spinelli,
Athina Geronikaki,
Elmira K. Hakobyan,
Harutyun Sahakyan,
Erik Arabyan,
Hovakim Zakaryan,
Lusine E. Nersesyan,
Anahit S. Aharonyan,
Irina S. Danielyan,
Rafayel E. Muradyan,
Anush A. Hovakimyan
Affiliations
Samvel N. Sirakanyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Domenico Spinelli
Dipartimento di Chimica G. Ciamician, Alma Mater Studiorum-Università di Bologna, Via F. Selmi 2, 40126 Bologna, Italy
Athina Geronikaki
School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Elmira K. Hakobyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Harutyun Sahakyan
Department of Bioengineering, Bioinformatics and Molecular Biology, Russian-Armenian University, 0051 Yerevan, Armenia
Erik Arabyan
Institute of Molecular Biology of NAS, Hasratyan 7, 0014 Yerevan, Armenia
Hovakim Zakaryan
Institute of Molecular Biology of NAS, Hasratyan 7, 0014 Yerevan, Armenia
Lusine E. Nersesyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Anahit S. Aharonyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Irina S. Danielyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Rafayel E. Muradyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
Anush A. Hovakimyan
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, 0014 Yerevan, Armenia
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.