Abstract

Background: α-Aminophosphonates are potentially biologically active species.

Objective: We wished to compare the synthetic methods and evaluate the effect of the α- aminophosphonates on sarcoma cell lines.

Methods: We investigated microwave-assisted Kabachnik–Fields and Pudovik reactions, as well as substitutions, and applied in vitro cytotoxicity screening.

Results: The Kabachnik–Fields condensation and the Pudovik reaction were found to be the most suitable regarding efficiency. Surprisingly, the multidrug resistant (MDR) uterine sarcoma (Mes-Sa/Dx5) cell line was the most susceptible to the aminophosphonates tested.

Conclusion: α-Aminophosphonates may indeed display anticancer effect. Substituents in the para position of the phenyl ring have an impact on the activity: the 4-Me and 4-Cl derivatives were more toxic to all cell lines as compared to the 4-H and 4-MeO species.

Keywords: α-Aminophosphonates, Kabachnik–Fields reaction, aza-Pudovik reaction, cytotoxicity, cancer, multidrug resistance, osteosarcoma, collateral sensitivity