A Lipophilic Pt(IV) Oxaliplatin Derivative Enhances Antitumor Activity

Aiman Abu Ammar, Raji Raveendran, Dan Gibson, Taher Nassar*, Simon Benita

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Side effects and acquired resistance by cancer cells limit the use of platinum anticancer drugs. Modification of oxaliplatin (OXA) into a lipophilic Pt(IV) complex [Pt(DACH)(OAc)(OPal)(ox)] (1), containing both lipophilic and hydrophilic axial ligands, was applied to improve performance and facilitate incorporation into polymeric nanoparticles. Complex 1 exhibited unique potency against a panel of cancer cells, including cisplatin-resistant tumor cells. [Pt(DACH)(OAc)(OPal)(ox)] incorporated nanoparticles (2) presented a mean diameter of 146 nm with encapsulation yields above 95% as determined by HPLC. Complexes 1 and 2 showed enhanced in vitro cellular Pt accumulation, DNA platination, and antiproliferative effect compared to OXA. Results of an orthotopic intraperitoneal model of metastatic ovarian cancer (SKOV-3) and a xenograft subcutaneous model of colon (HCT-116) tumor in SCID-bg mice showed that the activity of 1 and 2 significantly decreased tumor growth rates compared to control and OXA treatment groups. Consequently, these findings warrant further development toward clinical translation.

Original languageAmerican English
Pages (from-to)9035-9046
Number of pages12
JournalJournal of Medicinal Chemistry
Issue number19
StatePublished - 13 Oct 2016

Bibliographical note

Funding Information:
The authors gratefully acknowledge Prof. Reuven Reich for providing excellent technical assistance in orthotopic intraperitoneal model of metastatic ovarian cancer and Ofir Tirosh for long hours and hard work on the ICP-MS. D.G. thanks the Israel Science Foundation (Grant 1611/14) for partial support.

Publisher Copyright:
© 2016 American Chemical Society.


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