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

被引：22

作者：

Gandin, Valentina ^{[2
]}

Marzano, Cristina ^{[2
]}

Pelosi, Giorgio ^{[3
]}

Ravera, Mauro ^{[1
]}

Gabano, Elisabetta ^{[1
]}

Osella, Domenico ^{[1
]}

机构：

[1] Univ Piemonte Orientale, Dipartimento Sci & Innovaz Tecnol, I-15121 Alessandria, Italy

[2] Univ Padua, Dipartimento Sci Farmaco, I-35131 Padua, Italy

[3] Univ Parma, Dipartimento Chim, I-43124 Parma, Italy

来源：

CHEMMEDCHEM | 2014年 / 9卷 / 06期

关键词：

antitumor agents; chemoresistance; colon cancer; cytotoxicity; platinum complexes; CARCINOMA CELL-LINES; CRYSTAL-STRUCTURE; FLUOROURACIL-LEUCOVORIN; PLATINUM(IV) COMPLEXES; CARBOXYLATE COMPLEXES; 1ST-LINE TREATMENT; PHASE-II; ANTITUMOR; DRUG; RESISTANCE;

D O I：

10.1002/cmdc.201400061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1299 / 1305

页数：7

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