Synthesis and biological testing of 3,5-bis(arylidene)-4-piperidone conjugates with 2,5-dihydro-5H-1,2-oxaphospholenes

Abstract

Using the methodology of "click" chemistry, a series of conjugates of 3,5-bis(benzylidene)-1-(prop-2-yn)piperidin-4-ones with 4-alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5H-1,2 oxaphosphol 2-oxides was synthesized. All newly obtained compounds 8-18 were characterized by ¹H, ¹³C, ³¹P, ¹⁹F NMR and IR spectroscopy. The potential antitumor activity of the synthesized conjugates8-18was studied in terms of their ability to influence the viability of variouscancercell lines, including A549, SH-SY5Y, Hep-2, and HeLa. Compound 15, which contains two fluorine atoms in the benzene ring, was shown to be the most promising. The mechanism of the cytotoxic action of this conjugate is supposed to be associated with the ability to inhibit the glycolytic profile of transformed cells.

Keywords: 1,2,3-Triazole; 1,2-Oxaphospholene; Antitumor activity; Glycolysis; Heterocycles; Phosphorus; “Click” chemistry.