Stabilization of Cisplatin via Coordination of Ethylenediamine

Abstract

While the chemotherapeutic cisplatin is used to treat a variety of cancers, metal toxicity and cisplatin resistance via genetic and epigenetic changes limits its use and calls for alternative therapies. To combat the observed toxicities and create a more stable compound, which avoids isomerization into a trans configuration, three cisplatin analogues including cispalladium, dichloro-(ethylenediamine)-platinum(II), and dichloro-(ethylenediamine)-palladium(II) were synthesized as potential cisplatin alternatives. Each compound was evaluated for cytotoxicity on SK-OV-3 cells against cisplatin. Synthesis of dichloro-(ethylenediamine)-platinum(II) yielded 20.5% of the theoretical yield, while dichloro-(ethylenediamine)-palladium(II) yielded 49.1%. Results from the cytotoxicity trial revealed that cispalladium was not effective against SK-OV-3 cells, and dichloro-(ethylenediamine)-palladium had minimal effects. The dichloro-(ethylenediamine)-platinum(II) was the most efficacious with an IC50 value of 0.77 µg/ml compared to the IC50 of 0.61 µg/ml for cisplatin. With a similar IC50 to cisplatin, these results suggest that dichloro-(ethylenediamine)-platinum(II) has the potential to serve as a cisplatin alternative for cancer patients who develop resistance following their clinical course of cisplatin. Future studies on the cytotoxicity of dichloro-(ethylenediamine)-platinum(II) to induce cell death on cisplatin-resistance cell lines are necessary to determine the ability of the compound to be utilized as a cisplatin alternative. KEYWORDS: Cisplatin; Ovarian Cancer; SK-OV-3; Drug Resistance; Stability; Palladium; Ethylenediamine; Cispalladium; Dichloro-(ethylenediamine)-platinum(II); Dichloro-(ethylenediamine)-palladium(II)