Platinum(II)-acridines are a class of anticancer agents that effectively kill cancer cells at nanomolar concentrations, but also show unfavorable systemic toxicity when administered to test animals. The goal of this project was to convert the highly cytotoxic parent compound into a more tolerable prodrug. Platinum-based prodrugs typically comprise a Pt(IV) center and show an octahedral coordination geometry, which renders them chemically less reactive than the Pt(II) drugs. An example of this type of prodrug is cis,trans,cis-[PtCl2(OAc)2(NH3)(cyclohexylamine)], known as satraplatin, whose two axial acetato (OAc-) ligands confer a high degree of stability to the compound while in circulation. After entering cancer cells, a reduction reaction transforms the Pt(IV) back into the active Pt(II) form of the drug that then attaches to DNA to stall cancer cell replication. Thus, the significance of this work is to widen the therapeutic window of these anticancer agents. Oxidative addition reactions were performed with the Pt(II) prototype (1) to install axial ligands (compounds 2–4). High-performance liquid chromatography combined with mass spectrometry (LC-MS) was used to monitor the reactions and to assess compound purity. 1H NMR spectroscopy and X-ray crystallography were used to characterize the new complexes. Experiments mimicking the compounds’ bio-reduction chemistry under physiologically relevant conditions were also performed and the new compounds were tested in cell proliferation assays to assess their activity in cancer cell lines representing major classes of solid tumors.

Synthesis of platinum(IV)-acridine anticancer prodrugs

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.