Diethyl [(3-Phenoxy-2-Oxo-4-Phenyl-Azetidin-1-Yl)-Phenyl-Methyl]-Phosphonate As a Potent Anticancer Agent in Chemo-Differentiation Therapy of Acute Promyelocytic Leukemia Publisher Pubmed



Mohammadi S^{1, 2} ; Akbaribirgani S^{3, 4} ; Borji M³ ; Kaboudin B⁵ ; Vaezi M^{1, 2}
Source: European Journal of Pharmacology Published:2019

Abstract

Organophosphonates are a group of chemical agents which have high bioactivity. In the present study, we aimed to investigate the anticancer activity of the synthesized β-lactam derivatives of α-amino phosphonates on solid tumor and human leukemic cell lines. The results show that one of these compounds, Diethyl [(3-phenoxy-2-oxo-4-phenyl-azetidine-1-yl)-phenyl-methyl]-phosphonate, is a potent anticancer agent which especially shows anti-leukemic activity. Flow cytometry study showed that this chemical agent causes the G1 phase cell cycle arrest and consequently apoptosis in NB4 cell line as an acute promyelocytic leukemia model. In fact, this agent induces cell differentiation and apoptosis, at low and high concentrations, respectively. Its combination with All-Trans Retinoic Acid shows a higher percentage of cells in the terminal differentiation stage. This evidence suggested that diethyl phosphonate might be a proper candidate for chemo-differentiation therapy in acute promyelocytic leukemia and even in other types of acute myeloid leukemia. © 2019 Elsevier B.V.