Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety

•A series of novel α-aminophosphonate alizarins was designed and synthesized.•Many compounds showed better antiproliferative activities than the commercial anticancer drug 5-fluorouracil.•Representative compounds 7h, 7j and 7n may induce apoptosis through a mitochondrion-dependent pathway.

A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6–7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca2+ and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.

Graphical abstractA series of novel α-aminophosphonate derivatives containing alizarin moiety (6–7) was designed and synthesized as antitumor agents. Representative compounds 7h, 7j and 7n may induce apoptosis through a mitochondrion-dependent pathway.Figure optionsDownload full-size imageDownload as PowerPoint slide