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

58 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

Publisher Copyright:
© 2016 American Chemical Society.


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