trans,cis,cis-Bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV): a Prodrug Candidate for the Treatment of Oxaliplatin-Refractory Colorectal Cancer

The gold standard for the treatment of metastatic colorectal cancer consists of combination chemotherapy. Over time, however, the development of chemoresistant tumor clones leads to relapse. It may be possible to overcome oxaliplatin chemoresistance in colorectal cancer cells by exploiting a complex obtained from the insertion of the cyclohexane-1R,2R-diamine carrier ligand (the same diamine present in oxaliplatin) into an octahedral Pt^IV scaffold with high lipophilicity conferred by two benzoate axial ligands. Herein we report the synthesis, characterization (including X-ray structure), biological activity, and cellular accumulation of trans,cis,cis-bis(benzoato) dichlorido(cyclohexane-1R,2R-diamine)platinum(IV) complex in a panel of several human cancer cell lines, including a colon carcinoma cell line resistant to oxaliplatin. The compound under investigation shows the best performance in terms of in vitro anti-proliferative activity and ability to overcome chemoresistance, with respect to oxaliplatin and some other Pt^II reference complexes. This result is likely related to the high lipophilicity shown by the title compound that favors its cellular accumulation by passive diffusion. Colorectal cancer is targeted with a new platinum complex. The synthesis, characterization, anti-proliferative activity, and cellular accumulation of the complex trans,cis,cis-bis(benzoato)dichlorido(cyclohexane- 1R,2R-diamine)platinum(IV) is reported. The title compound was found to be very cytotoxic on all the human cancer cell lines tested, including a colon carcinoma cell line resistant to oxaliplatin.