Cytotoxic Activity of α-Aminophosphonic Derivatives Coming from the Tandem Kabachnik-Fields Reaction and Acylation

Encouraged by the significant cytotoxic activity of simple a-aminophosphonates, a molecular library comprising phosphonoylmethyl- and phosphinoylmethyl-a-aminophosphonates, a tris derivative, and N-acylated species was established. The promising aminophosphonate derivatives were subjected to a comparative structure-activity analysis. We evaluated 12 new aminophosphonate derivatives on tumor cell cultures of different tissue origins (skin, lung, breast, and prostate). Several derivatives showed pronounced, even selective cytostatic effects. According to IC50 values, phosphinoylmethyl-aminophosphonate derivative 2e elicited a significant cytostatic effect on breast adenocarcinoma cells, but it was even more effective against prostatic carcinoma cells. Based on our data, these new compounds exhibited promising antitumor activity on different tumor types, and they might represent a new group of alternative chemotherapeutic agents.

Automated summary

Motivated by the cytotoxicity of a-aminophosphonates, a library of various derivatives was established and evaluated on tumor cells of different tissue origins. Some derivatives showed selective cytostatic effects, with phosphinoylmethyl-aminophosphonate derivative 2e exhibiting significant activity against breast and prostate cancer cells. These new compounds hold promise as alternative chemotherapeutic agents against different tumor types.