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trans , cis , cis ‐Bis(benzoato)dichlorido(cyclohexane‐1 R ,2 R ‐diamine)platinum(IV): a Prodrug Candidate for the Treatment of Oxaliplatin‐Refractory Colorectal Cancer
Author(s) -
Gandin Valentina,
Marzano Cristina,
Pelosi Giorgio,
Ravera Mauro,
Gabano Elisabetta,
Osella Domenico
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201400061
Subject(s) - oxaliplatin , lipophilicity , prodrug , diamine , chemistry , ligand (biochemistry) , platinum , cyclohexane , stereochemistry , folfox , cancer research , colorectal cancer , cancer , biochemistry , medicine , biology , organic chemistry , receptor , catalysis
Abstract 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‐1 R ,2 R ‐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‐1 R ,2 R ‐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.