Original Articles
Sthefany Mendoza-Espinosa, Bal
Abstract
Organophosphates compounds have important medical applications including anti-cancer and anti-viral activity. Particularly, phosphoramidates derivatives, characterized by the presence of a nitrogen-phosphorous-oxygen group (N-P=O), have demonstrated a selective cytotoxic effect against several cancer cells lines. Although the effect of several other phosphonates had been tested, phosphoramidate (bisphosphoramidates) have not been evaluated and their properties remain unexplored. Thus, the focus of this investigation was to synthetize a series of bisphosphoramidates to test their cytotoxic effect against the A549 human lung adenocarcinoma cell line. The synthesis of the title compounds was easily achieved adapting the synthetic route described by Kim et al. using three commercially available diamines. Once the compounds were purified and fully characterized, their cytotoxic activity was assessed using the MTT assay at a fixed concentration. From them, only one bisphosphoramidate derivative, named tetraphenyl propane diphosphoramidate (compound 5), was unknown and therefore was fully characterized by solution NMR spectroscopic techniques and mass spectrometry. The spectroscopic analyses of the rest of the compounds perfectly matched the previously reported data. Among the tested compounds, tetraphenyl ethylene diphosphoramidate (compound 4), showed the best cytotoxic effect against the cellular line with similar toxicity to that shown from the drug cisplatin. To the best of our knowledge this is the first time that the anti-cancer effect of the bisphosphoramidates is reported. We are currently synthetizing new bisphosphoramidates which anti-cancer activity would be evaluated against several cancer cell lines to determine their specificity.