Investigator: Chin Hin Leung, Rhode Island College

Scientific Theme: Molecular Toxicology & Cancer

Abstract: The proposed research will synthesize a new family of metal complexes with incorporated phosphonium groups. The new compounds are expected to shed light on the synergistic effects of tumor-cell selective phosphonium groups and DNA-binding metal complexes. Two subtypes of the novel motif will be made, the first type based on the square-planar platinum center as found in the FDA approved cancer drugs cisplatin, carboplatin and oxaliplatin, with an added phosphonium group linked to the complex through the chelating diamine ligand. The second subtype is based on a DNA intercalating palladium compound, in which a phosphonium group is attached to the planar heterocyclic ligand. Upon synthesis and characterization, DNA binding studies will be performed to evaluate the effects of the added phosphonium groups. The studies will shed light on the incorporation of phosphonium groups as a strategy to enhance the cellular uptake and overcome resistance in platinum and other precious-metal based anticancer compounds.

Human Health Relevance: The proposed research will contribute to further understanding of platinum-based anticancer drugs.