title: Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans.
abstract: 1. To determine the ability of fungi to metabolize sulphur- and oxygen-containing azaarenes, Cunninghamella elegans ATCC 9245 was grown in 125-ml flasks containing fluid Sabouraud medium. The cultures and controls were incubated at 28 degrees C with shaking and dosed with 16.7 mM phenothiazine or phenoxazine. After incubation for 72h, the mycelia and filtrates were extracted with ethyl acetate and the combined residues analysed by high-performance liquid chromatography. Residual phenothiazine and phenoxazine were 21 and 22%, respectively, of the total UV absorbance at 254 nm. 2. The metabolites were identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. The fungus oxidized phenothiazine to phenothiazine sulphoxide, 3-hydroxyphenothiazine sulphoxide, phenothiazin-3-one, and 3-hydroxyphenothiazine and oxidized phenoxazine to phenoxazin-3-one. 3. Three of the four compounds produced by C. elegans from phenothiazine were identical to those produced by mammals, supporting the use of the fungus as a microbial model for drug metabolism.
authors.affiliation: National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA. jsutherland@nctr.fda.gov
authors.forename: J B
authors.initials: JB
authors.lastname: Sutherland
authors.forename: J P
authors.initials: JP
authors.lastname: Freeman
authors.forename: T M
authors.initials: TM
authors.lastname: Heinze
authors.forename: J D
authors.initials: JD
authors.lastname: Moody
authors.forename: I A
authors.initials: IA
authors.lastname: Parshikov
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
authors.forename: D
authors.initials: D
authors.lastname: Zhang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D020093:Cunninghamella / Q000378:metabolism*; D010078:Oxazines / Q000378:metabolism*; D010084:Oxidation-Reduction; D010640:Phenothiazines / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013454:Sulfoxides / Q000378:metabolism
chemical_list: D010078:Oxazines; D010640:Phenothiazines; D013454:Sulfoxides; C039203:phenoxazine; C031637:phenothiazine