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.
Identifer | oai:union.ndltd.org:pdx.edu/oai:pdxscholar.library.pdx.edu:open_access_etds-3085 |
Date | 06 November 2014 |
Creators | Kendrick, Kelsie Lynn |
Publisher | PDXScholar |
Source Sets | Portland State University |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | Dissertations and Theses |
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