First Advisor

David Peyton

Date of Publication

Fall 11-6-2014

Document Type

Thesis

Degree Name

Master of Science (M.S.) in Chemistry

Department

Chemistry

Language

English

Subjects

Chloroquine -- Oxidation, Chloroquine -- Metabolism, Antimalarials -- Development

DOI

10.15760/etd.2083

Physical Description

1 online resource (vi, 82 pages)

Abstract

The aim of this study was to elucidate the oxidation products of a candidate antimalarial drug, PL69, using a porphyrin system and to determine the accuracy of the oxidation products produced, as compared to what is expected in metabolism. PL69 is a reversed chloroquine (RCQ) that is active against chloroquine resistant malaria. Porphyrin oxidation systems have been shown to mimic in vitro enzymatic metabolism reactions. PL69 and its known metabolite, PL16, were incubated with the porphyrin system, and then the oxidation products were collected and separated by HPLC. The oxidation products were characterized by NMR and mass spectrometry and compared to previous metabolism studies of PL69 with liver microsomes. The results of this research show that this porphyrin system is an acceptable mimic of in vitro metabolism methods for RCQs and provides a good framework for understanding the types of metabolism that will occur in vivo for RCQs.

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Persistent Identifier

http://archives.pdx.edu/ds/psu/13195

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