Microbial production of phase I and phase II metabolites of propranolol.
1. The production in multimilligram amounts of 4- and 5-hydroxylated metabolites of (R)- or (S)-propranolol by biotransformation with two fungal strains, an Absidia sp. M50002 and a Cunninghamella sp. M50036, was carried out, starting from either the racemic drug or pure enantiomers. 2. While both enantiomers of propranolol were hydroxylated in the 5-position by incubation with strain M50002, the strain M50036 operated a chiral discrimination, resulting in the exclusive formation of the 4-hydroxy-(R)-enantiomer. 3. In addition, a Streptomyces sp. strain M52104, isolated from a soil sample, was selected for the high-yield regioselective β-glucuronidation of propranolol and its 4- and 5-hydroxylated derivatives. 4. NMR and mass spectroscopic data have been extensively used for the unambiguous characterization of 4- and 5-hydroxylated and glucuronidated derivatives, all of them corresponding to the major animal and human metabolites of propranolol, a typical substrate of CYP2D6.
Bertin-Pharma, 10bis avenue Ampère, Zone d'activités du Pas du Lac, Montigny-le-Bretonneux, France.
Cyrille
C
Marvalin
Robert
R
Azerad
D020095:Absidia / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism*; D011433:Propranolol / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D011433:Propranolol