Electronic Theses and Dissertations

Date of Award

2019

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Chalet Tan

Second Advisor

Walter Chambliss

Third Advisor

Seongbong Jo

Relational Format

dissertation/thesis

Abstract

Small molecules functioning as negative regulators of MDM2 have been considered as promising anti-cancer agents. A series of novel anthraquinone (AQ) analogues upregulate p53, a well-known tumor suppressor, by inactivating its antagonist protein MDM2. The novel AQ compounds synthesized through the modifications on the rhein scaffold were reported to have successfully arrested tumor growth. To have a better understanding of their underlying metabolism in vivo, pharmacokinetic (PK) studies were performed for the AQ compounds. A selective, accurate and reproducible assay methodology for PK study was set up for each AQ compound. The stabilities of AQ compounds were then evaluated in terms of different pharmacokinetic properties. All AQ compounds were found unstable in plasma or eliminated from the systemic circulation in mice rapidly possibly due to their structural instability or rapid hepatic metabolism. The correlation between in-vitro stability and in-vivo metabolism can give a good guide for future PK studies.

Available for download on Tuesday, September 22, 2020

Included in

Pharmacology Commons

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