Western Kentucky University
The Leaving Ligand Structure of Platinum Compounds impacts the Survival of Human Embryonic Kidney and Melanoma Cells
Grade Level at Time of Presentation
Senior
Major
Chemistry
Minor
Biology
KY House District #
1
KY Senate District #
3
Faculty Advisor/ Mentor
Blairanne Williams, PhD
Department
Chemistry
Abstract
Since the discovery of the toxic properties of platinum compounds, three platinum-based chemotherapeutics have been approved by the FDA for the treatment of various cancers. Platinum-based drugs are given to approximately half of all patients who receive chemotherapeutic treatment, indicating their importance. The FDA-approved chemotherapeutics and novel compounds, Dichloro(ethylenediamine)platinum(II) (Pt(en)Cl2) and 1,1-cyclobutanedicarboxylic acid (ethylenediamine)platinum(II) (Pt(en)CBDCA) used in this study contain a central platinum(II) atom with two separate groups attached, a leaving ligand and nonleaving ligand. The novel compounds share a non-leaving ligand, ethylenediamine, that remains attached to the platinum when it enters the cell. The leaving ligands that detach from the platinum atom once in the cell differ, allowing us to test the role of the structure. The leaving ligand of Pt(en)Cl2 has two chlorine atoms that can be displaced from the molecular structure independently. In contrast, Pt(en)CBDCA has one cyclobutanedicarboxylato group whose two platinum bonds are displaced simultaneously. How cisplatin-like complexes kill cells is well-documented in the scientific literature. However, the impact of leaving ligand structure on cell survival is unknown. To test the hypothesis that differences in leaving ligand structure of platinum(II) complexes influence toxicity, human embryonic kidney cells (HEK293) and melanoma cells (SKMEL5) were individually exposed to increasing concentrations of Pt(en)Cl2 or Pt(en)CBDCA for 24 hours. The data reported as the half-maximal inhibitory concentration of the drug (IC50) indicates a significant impact of leaving ligand structure on cell survival with an IC50 of 36.67 µM for Pt(en)Cl2 and an IC50 of 55.88 µM for Pt(en)CBDCA for HEK293 cells. The data indicate an even more influential effect caused by differences in leaving ligand structure in SKMEL5 melanoma cells, with a calculated IC50 of 12.5 µM for Pt(en)Cl2 and an IC50 of 108.52 µM for Pt(en)CBDCA, indicating that the leaving ligand of Pt(en)Cl2 is more toxic.
The Leaving Ligand Structure of Platinum Compounds impacts the Survival of Human Embryonic Kidney and Melanoma Cells
Since the discovery of the toxic properties of platinum compounds, three platinum-based chemotherapeutics have been approved by the FDA for the treatment of various cancers. Platinum-based drugs are given to approximately half of all patients who receive chemotherapeutic treatment, indicating their importance. The FDA-approved chemotherapeutics and novel compounds, Dichloro(ethylenediamine)platinum(II) (Pt(en)Cl2) and 1,1-cyclobutanedicarboxylic acid (ethylenediamine)platinum(II) (Pt(en)CBDCA) used in this study contain a central platinum(II) atom with two separate groups attached, a leaving ligand and nonleaving ligand. The novel compounds share a non-leaving ligand, ethylenediamine, that remains attached to the platinum when it enters the cell. The leaving ligands that detach from the platinum atom once in the cell differ, allowing us to test the role of the structure. The leaving ligand of Pt(en)Cl2 has two chlorine atoms that can be displaced from the molecular structure independently. In contrast, Pt(en)CBDCA has one cyclobutanedicarboxylato group whose two platinum bonds are displaced simultaneously. How cisplatin-like complexes kill cells is well-documented in the scientific literature. However, the impact of leaving ligand structure on cell survival is unknown. To test the hypothesis that differences in leaving ligand structure of platinum(II) complexes influence toxicity, human embryonic kidney cells (HEK293) and melanoma cells (SKMEL5) were individually exposed to increasing concentrations of Pt(en)Cl2 or Pt(en)CBDCA for 24 hours. The data reported as the half-maximal inhibitory concentration of the drug (IC50) indicates a significant impact of leaving ligand structure on cell survival with an IC50 of 36.67 µM for Pt(en)Cl2 and an IC50 of 55.88 µM for Pt(en)CBDCA for HEK293 cells. The data indicate an even more influential effect caused by differences in leaving ligand structure in SKMEL5 melanoma cells, with a calculated IC50 of 12.5 µM for Pt(en)Cl2 and an IC50 of 108.52 µM for Pt(en)CBDCA, indicating that the leaving ligand of Pt(en)Cl2 is more toxic.