Publication Date

Spring 2020

Advisor(s) - Committee Chair

Blairanne Williams (Director), Kevin Williams, and Lester Pesterfield

Degree Program

Department of Chemistry

Degree Type

Master of Science

Abstract

There are currently three FDA platinum compounds approved for use as chemotherapeutics, where each drug has variable efficacies for different cancer types depending on cancer’s tissue of origin. The approved compounds are platinum(II) complexes with four coordination sites on the platinum atom allowing two types of ligands to attach: leaving ligands, which are removed from the platinum atom in solution, and non-leaving ligands, which remain complexed to the platinum. Carboplatin, the preferred compound used to treat ovarian and small-cell lung cancers, has a characteristic cyclobutanedicarboxylic acid leaving ligand and two ammonia non-leaving ligands. A novel compound, 1,1-cyclobutanedicarboxylato(ethylenediamine)platinum (II), or Pt(en)CBDCA, has an ethylenediamine group in place of the ammonia ligands. We hypothesize that the efficacies of platinum compounds vary due to differences in the ligands. To understand the impact of these structural changes, we are investigating the analogue’s effects on cell viability by assessing cell survival in human cancer cell lines. The data shows a difference in cellular response of the melanoma and small cell lung cells treated with both Carboplatin and Pt(en)CBDCA. Given that intracellular accumulation is typically correlated to toxicity, we hypothesize that structural differences may alter intracellular accumulation of the compounds. To test our hypothesis, we are examining intracellular levels of both carboplatin and Pt(en)CBDCA using atomic absorption spectroscopy. In this study, we aim to correlate the intracellular concentration of platinum with cell survival response to create a toxicity profile of these compounds.

Disciplines

Biochemistry | Cancer Biology | Pharmacology, Toxicology and Environmental Health

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