title: Microbial biotransformation of the angiotensin II antagonist GR117289 by Streptomyces rimosus to identify a mammalian metabolite.
abstract: Screening a range of microorganisms incubated with the angiotensin II antagonist GR117289 resulted in the use of Streptomyces rimosus to generate five related biotransformation products. These comprised three compounds hydroxylated on the aliphatic side chain, one further oxidized to a ketone, and one hydroxylated on the phenyl ring. These microbial metabolites were used as standards to identify a human metabolite detected in plasma and urine, but present in insufficient quantities for full structural characterisation. This further demonstrates how the use of microbial biotransformation systems at an early stage of drug metabolism studies can act as a valuable tool in facilitating identification of minor human metabolites.
authors.affiliation: Natural Products Department, Glaxo Research and Development Limited, Greenford, Middlesex, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cannell
authors.forename: A R
authors.initials: AR
authors.lastname: Knaggs
authors.forename: M J
authors.initials: MJ
authors.lastname: Dawson
authors.forename: G R
authors.initials: GR
authors.lastname: Manchee
authors.forename: P J
authors.initials: PJ
authors.lastname: Eddershaw
authors.forename: I
authors.initials: I
authors.lastname: Waterhouse
authors.forename: D R
authors.initials: DR
authors.lastname: Sutherland
authors.forename: G D
authors.initials: GD
authors.lastname: Bowers
authors.forename: P J
authors.initials: PJ
authors.lastname: Sidebottom
mesh_terms: D057911:Angiotensin Receptor Antagonists; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009539:Nicotinic Acids / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D011854:Radiochemistry; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000378:metabolism*; D013777:Tetrazoles / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D057911:Angiotensin Receptor Antagonists; D002250:Carbon Radioisotopes; D009539:Nicotinic Acids; D013777:Tetrazoles; C078790:GR 117289