Microbial models of mammalian metabolism. N-dealkylation of furosemide to yield the mammalian metabolite CSA using Cunninghamella elegans.
Furosemide (Lasix), a widely used diuretic, is metabolized by the fungus Cunninghamella elegans (ATCC 36112) to 4-chloro-5-sulfamoyl anthranilic acid (CSA), a metabolite also present in mammalian systems. This metabolite was isolated following preparative-scale incubations of C. elegans, and was characterized by comparison with standard CSA using 13C-NMR, mass spectrometry (high-resolution mass spectra, electron impact mass spectra), UV, TLC, and HPLC with fluorescence detection. Because a known complication with furosemide studies is the spontaneous formation of CSA by decomposition of furosemide during incubation, extraction, and/or analysis, a time course study was conducted to determine the rate of CSA formation caused by metabolism vs. the relatively low rate of CSA formation caused by spontaneous decomposition.
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Texas, Austin 78712-1074.
M
M
Hezari
P J
PJ
Davis
D001711:Biotransformation; D003640:Dealkylation; D005665:Furosemide / Q000493:pharmacokinetics*; D009090:Mucorales / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000378:metabolism*
D062367:ortho-Aminobenzoates; D005665:Furosemide; C010554:4-chloro-5-sulfamoylanthranilic acid