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Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans
Date Issued
2016-08-19
Date Available
2019-07-01T13:40:58Z
Abstract
1.Fluorine plays a key role in the design of new drugs and recent FDA approvals included two fluorinated drugs, tedizolid phosphate and vorapaxar, both of which contain the fluorophenyl pyridyl moiety. 2.To investigate the likely phase-I (oxidative) metabolic fate of this group, various fluorinated phenyl pyridine carboxylic acids were incubated with the fungus Cunninghamella elegans, which is an established model of mammalian drug metabolism. 3.19F NMR spectroscopy established the degree of biotransformation, which varied depending on the position of fluorine substitution, and gas chromatography–mass spectrometry (GC–MS) identified alcohols and hydroxylated carboxylic acids as metabolites. The hydroxylated metabolites were further structurally characterised by nuclear magnetic resonance spectroscopy (NMR), which demonstrated that hydroxylation occurred on the 4′ position; fluorine in that position blocked the hydroxylation. 4.The fluorophenyl pyridine carboxylic acids were not biotransformed by rat liver microsomes and this was a consequence of inhibitory action, and thus, the fungal model was crucial in obtaining metabolites to establish the mechanism of catabolism.
Sponsorship
European Commission - Seventh Framework Programme (FP7)
Type of Material
Journal Article
Publisher
Taylor & Francis
Journal
Xenobiotica
Volume
47
Issue
9
Start Page
763
End Page
770
Copyright (Published Version)
2016 Informa UK
Language
English
Status of Item
Peer reviewed
ISSN
0049-8254
This item is made available under a Creative Commons License
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