Synthesis of conjugates of (−)-cytisine derivatives with ferrocene-1-carbaldehyde and their cytotoxicity against HEK293, Jurkat, A549, MCF-7 and SH-SY5Y cells

Abstract

First example of conjugation of quinolizidine alkaloids with ferrocene was presented. The cytotoxic properties of the obtained conjugates against cell lines НЕК293, Jurkat, A549, MCF-7 and SH-SY5Y were studied. It was found, that conjugate 17 (having ferrocenyl methylene fragment and phenyl carboxamide moiety) produced a relatively higher cytotoxicity towards cancer Jurkat and SH-SY5Y cells with weak activity against non-cancerous HEK293 cells, suggesting the selectivity of this substance to inhibit certain tumor cells. The effect of leading compound 17 on cell cycle progression of HEK293, Jurkat, A549, MCF-7 and SH-SY5Y lines in a time-dependent fashion was studied. It was shown that hit-compound 17 caused a prominent arrest of MCF-7, Jurkat and A-549 cells in S phase along with a decrease of cells in G1 and a nearly total decline of cells in G2/M; the induction of apoptosis in HEK293 and SH-SY5Y cells was cell-cycle independent.