Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans
|Title:||Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans||Authors:||Palmer-Brown, William; Dunne, Brian; Ortin, Yannick; Murphy, Cormac D.; et al.||Permanent link:||http://hdl.handle.net/10197/10828||Date:||19-Aug-2016||Online since:||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.||Funding Details:||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||Keywords:||Cytochrome P450; Cunninghamella; Carboxylic Acids; Lactones; Oxazoles; Pyridines; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy; Fluorine; Mass Spectrometry; Gas Chromatography-Mass Spectrometry; Microbial model; 19F NMR||DOI:||10.1080/00498254.2016.1227109||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Biomolecular and Biomedical Science Research Collection|
Show full item record
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.