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 PtIV 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 PtII reference complexes. This result is likely related to the high lipophilicity shown by the title compound that favors its cellular accumulation by passive diffusion.

trans,cis,cis-Bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV): a Prodrug Candidate for the Treatment of Oxaliplatin-Refractory Colorectal Cancer / Valentina, Gandin; Cristina, Marzano; Pelosi, Giorgio; Mauro, Ravera; Elisabetta, Gabano; Domenico, Osella. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 9:(2014), pp. 1299-1305. [10.1002/cmdc.201400061]

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

PELOSI, Giorgio;
2014-01-01

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-1R,2R-diamine carrier ligand (the same diamine present in oxaliplatin) into an octahedral PtIV 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 PtII reference complexes. This result is likely related to the high lipophilicity shown by the title compound that favors its cellular accumulation by passive diffusion.
2014
trans,cis,cis-Bis(benzoato)dichlorido(cyclohexane-1R,2R-diamine)platinum(IV): a Prodrug Candidate for the Treatment of Oxaliplatin-Refractory Colorectal Cancer / Valentina, Gandin; Cristina, Marzano; Pelosi, Giorgio; Mauro, Ravera; Elisabetta, Gabano; Domenico, Osella. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 9:(2014), pp. 1299-1305. [10.1002/cmdc.201400061]
File in questo prodotto:
File Dimensione Formato  
Gandin2014.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 286.86 kB
Formato Adobe PDF
286.86 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2732300
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 23
social impact