Date of Award

8-2022

Document Type

Thesis

Department

Chemistry

First Advisor

Denana Miodragovic, Ph.D.

Abstract

The pursuit of novel platinum(II)-based drugs has been driven by adverse side effects and resistance to current FDA-approved antineoplastic platinum drugs, such as cisplatin. The discovery of a synergistic effect between the FDA-approved anticancer drugs arsenic trioxide and cisplatin in vitro inspired the synthesis of complexes containing the moieties of both drugs. Arsenoplatins (APs) are novel and promising chemotherapeutic agents with an arsenous acid moiety attached to a platinum(II) center. Based on the NCI-60 (NCI = National Cancer Institute) screen, the first member of the family, arsenoplatin-1 (AP-1), has shown greater cytotoxicity than cisplatin or arsenic trioxide in various cancer cell lines. The focus of this study is to test the stability of arsenoplatins in a physiological saline solution that is necessary for future in vivo studies. A Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) was used to determine the stability of APs 1-7 in physiological saline solution (pH=7.40 ±0.05) at room temperature and 37oC. The results of this study have shown that among the seven arsenoplatins tested, AP-1, AP-5, and AP-7, which contain deprotonated acetamides as chelate rings, are more stable than AP-2 and AP-4, which contain deprotonated propanamide rings. AP-3 and AP-6 are the only arsenoplatins that exist as linkage isomers in the solution. The stability of AP-1 in physiological saline was also tested at body temperature (37°C). The RP-HPLC method was validated for linearity by performing a linear regression analysis. Based on the results of this study, AP-1, AP-5, and AP-7 are the most stable of the arsenoplatins tested in physiological saline solution and represent the best candidates for planned in vivo studies.

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