Abstract
Recently, it was found that the carbonyl group of 1-[3-(4-phenoxyphenoxy)-2-oxopropyl]indole-5-carboxylic acid (5), an inhibitor of the pro-inflammatory enzyme cytosolic phospholipase A2 α, is easily reduced by rat liver S9 fractions in vitro. Determination of the inhibitory potency of certain putative inhibitors of carbonyl reducing enzymes on the transformation of the ketone derivative 5 to its alcohol 6 by recombinant microsomal NADPH-cytochrome P450 reductase and by recombinant cytosolic carbonyl reductase-1 now reveals that these compounds show a lack of specificity for these two enzymes in part. Thus, an assignment of the roles of different carbonyl reductases in metabolic keto reduction by the use of inhibitors is problematic. In addition, the ability of NADPH-cytochrome P450 reductase and carbonyl reductase-1 to reduce the ketone groups of the drugs haloperidol and daunorubicin was examined. Under the conditions applied, a pronounced reductive metabolism was only observed for daunorubicin in the presence of microsomal NADPH-cytochrome P450 reductase. Similarly, in rat liver S9 fractions a marked reduction of daunorubicin was seen, while haloperidol was only slightly metabolized to its alcohol. After separation of the S9...Continue Reading
References
Sep 25, 1995·Biochemical and Biophysical Research Communications·I A SlepnevaV V Khramtsov
Jul 17, 1995·Biochemical Pharmacology·H OharaA Hara
Sep 28, 1993·Biochemistry·D G Tew
Oct 17, 1998·Biochemical Pharmacology·J J McGuireB M Bennett
Dec 28, 1999·Biochemical Pharmacology·U Breyer-Pfaff, K Nill
Jan 11, 2000·Clinical Pharmacokinetics·S Kudo, T Ishizaki
Apr 27, 2000·Toxicology·U C Oppermann, E Maser
Apr 18, 2001·Chemico-biological Interactions·A Atalla, E Maser
Jul 7, 2005·Basic & Clinical Pharmacology & Toxicology·Jaroslaw DudkaMarek Murias
Dec 31, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hans-Jörg MartinEdmund Maser
Dec 31, 2005·Cardiovascular Toxicology·Andrew SlupeHenry A Charlier
Jan 5, 2006·Annals of Nutrition & Metabolism·Jaroslaw Dudka
Mar 21, 2006·Drug Metabolism and Pharmacokinetics·Toshiyuki MatsunagaAkira Hara
Mar 7, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ryan H TakahashiK Wayne Riggs
May 7, 2008·Cancer·Javier G BlancoSmita Bhatia
Jul 19, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nina KassnerLeszek Wojnowski
Feb 11, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Onkar S BainsK Wayne Riggs
Dec 17, 2009·Bioorganic & Medicinal Chemistry·Laura ForsterMatthias Lehr
Feb 23, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zeen TongJoAnn Scatina
Jun 30, 2010·Journal of Medicinal Chemistry·Andreas DrewsMatthias Lehr
Oct 15, 2010·Current Drug Metabolism·Petra MalátkováVladimír Wsól
Dec 21, 2011·Drug Metabolism Reviews·Lucie Skarydová, Vladimír Wsól
Sep 18, 2012·European Journal of Medicinal Chemistry·Davide PirolliMaria Cristina De Rosa
Sep 1, 2005·Current Protocols in Toxicology·M Jane Cox Rosemond
Dec 4, 2012·Chemico-biological Interactions·Bengt Persson, Yvonne Kallberg
Oct 15, 2013·Chemico-biological Interactions·Jörg FabianMatthias Lehr