Synthesis and study of antitumor activity of 4H-pyrano[3,2-c]pyridines based on N-(2-azidoethyl)- and N-propargyl-3,5-bis(arylidene)piperidin-4-ones

• Published in: Russian chemical bulletin Vol. 66; no. 1; pp. 104 - 110
• Main Authors: Bykhovskaya, O. V., Aladzheva, I. M., Makarov, M. V., Rybalkina, E. Yu, Klemenkova, Z. S., Brel, V. K.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2017; Springer Nature B.V
• Subjects: Anticancer properties; Assaying; Biotechnology; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Cytotoxicity; Design modifications; Full Articles; In vitro testing; Inorganic Chemistry; Malononitrile; Nitrogen; Organic Chemistry; Pyridines; Synthesis; Toxicity; pyrano[3,2; 1,5-diaryl-3-oxo-1,4-pentadienes; pyridines; 4; antitumor activity; 3,5-bis(arylidene)piperidin-4-ones
• ISSN: 1066-5285; 1573-9171
• DOI: 10.1007/s11172-017-1707-x

The synthesis of 3,5-bis(arylidene)piperidin-4-ones containing the 2-azidoethyl (azides 1a – d ) or propargyl (acetylenes 2a – c ) group at the nitrogen atom of the 4-piperidinone ring was described. The in vitro MTT assay for cytotoxicity of these compounds toward the human tumor cell lines PC3, HCT116, and MCF7 and the human embryonic kidney cells HEK293 revealed that N -(2-azidoethyl)-3,5-bis(3-pyridylidene)piperidin-4-one ( 1c ) and N -propargyl-3,5- bis(benzylidene)piperidin-4-one ( 2a ) exhibit high activity (IC 50 in the range of 1–5 μmol L –1 ). The reaction of compounds 1a – d and 2a – c with malononitrile affords the corresponding 4 H -pyrano[3,2- c ]pyridines 3a – d and 4a – c devoid of cytotoxicity. This is evidence of the importance of preserving the 1,5-diaryl-3-oxo-1,4-pentadiene moiety upon the modification of 3,5-bis(arylidene)piperidin-4-ones in drug design when searching for new antitumor agents based on these compounds.