In vitro assessment of cytotoxicity and biotransformation of propranolol in Cunninghamella echinulata.
1. Biotransformation studies with five concentrations of racemic propranolol were conducted using the filamentous fungus Cunninghamella echinulata ATCC 9244. 2. The rate of formation and subsequent disappearance of a new major metabolite, 8-hydroxypropranolol, was dose-dependent. Desisopropylpropranolol and 4-hydroxypropranolol were also formed. 4-Hydroxypropranolol was the major fungal metabolite in earlier studies. 3. Propranolol exerted a dose-dependent response on biotransformation, fungal growth, dextrose utilization, ammonia formation and incubation broth pH. Determination of dextrose utilization and incubation broth pH would provide reliable, cost-effective and convenient alternative methods for cytotoxicological evaluation.
Foster
B C
BC
Bureau of Drug Research, Health Protection Branch, Ottawa, Ontario, Canada.
Litster
D L
DL
Wilson
D L
DL
Ormsby
E
E
Dawson
B A
BA
D000641:Ammonia / Q000378:metabolism; D001711:Biotransformation; D002852:Chromatography, Ion Exchange; D003603:Cytotoxins / Q000633:toxicity*; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009090:Mucorales / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000493:pharmacokinetics / Q000633:toxicity*; D013237:Stereoisomerism
D003603:Cytotoxins; D000641:Ammonia; D011433:Propranolol; D005947:Glucose