Synthesis, Characterization, and Cytotoxicity of Dicycloalkylaminepyrophosphatoplatinum(II) Complexes

High Resolution Image Download MS PowerPoint Slide Platinum complexes have now been used in chemotherapy regimens for almost half a century to treat a variety of cancers. The most clinically significant of these compounds to date is cisplatin, cis -diamminedichloroplatinum(II), whose clinical application has significantly reduced the mortality rate of several cancers. Despite this development, there is still a push to find new compounds that have improved efficacy, that can be administered at lower doses, and that produce less severe side-effects compared to current options. One class of molecules that may fill that role is phosphaplatins, an underexplored class of platinum(II) complexes that contain a bidentate pyrophosphate ligand. These compounds are anionic at physiological pH and display reduced DNA-binding compared to cisplatin. This study expands on the list of known phosphaplatins by introducing two new compounds, dicyclobutylaminedihydrogenpyrophosphatoplatinum(II) and dicyclopentylaminedihydrogenpyrophosphatoplatinum(II). Here we report complete synthetic details, as well as cell viability data in response to these compounds using two cancer cell lines, a human lung adenocarcinoma and a triple-negative human breast cancer. While these compounds inhibit cell viability less than the leading phosphaplatin drug candidate, trans -(1 R,2 R )-diaminocyclohexanedihydrogenpyrophosphatoplatinum(II), this work represents an important step in elucidating structure–activity relationships for this class of molecules.