Inhibition of rat liver cytochrome P450 isozymes by isothiocyanates and their conjugates: a structure-activity relationship study

Carcinogenesis
C C ConawayF L Chung

Abstract

A series of arylalkyl and alkyl isothiocyanates, and their glutathione, cysteine, and N-acetylcysteine conjugates were used to study their inhibitory activity toward the dealkylation of ethoxyresorufin (EROD), pentoxyresorufin (PROD), and methoxyresorufin (MROD) in liver microsomes obtained from the 3-methylcholanthrene or phenobarbital-treated rats. These reactions are predominantly mediated by cytochrome P450 (P450) isozymes 1A1 and 1A2, 2B1 and 1A2, respectively. All isothiocyanates inhibited PROD more readily than EROD. Increases in the alkyl chain length of arylalkyl isothiocyanates to C6 resulted in an increased inhibitory potency in these assays; at longer alkyl chain lengths (C8-C10) the inhibitory potency declined. The IC50s for phenethyl isothiocyanate (PEITC) were 47, 46 and 1.8 microM for EROD, MROD and PROD, respectively. Substitution of an additional phenyl group on PEITC also increased the inhibitory potency; the IC50s for 1,2-diphenylethyl isothiocyanate (1,2-DPEITC) and 2,2-diphenylethyl isothiocyanate (2,2-DPEITC) were 0.9 and 0.26 microM for EROD, and 0.045 and 0.13 microM for PROD, respectively. The relative inhibitory potency of PEITC and its conjugates was N-acetylcysteine-PEITC (PEITC-NAC) < glutathione-P...Continue Reading

Citations

May 15, 2001·International Journal of Cancer. Journal International Du Cancer·M A LeaC desBordes
Dec 6, 2005·Cell Biology and Toxicology·T W SchultzM Woldemeskel
Feb 22, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Asaka TakahashiYasushi Uda
May 7, 2009·Acta Pharmacologica Sinica·Xiang WuKe Xu
May 8, 2010·Antioxidants & Redox Signaling·John D HayesAlbena T Dinkova-Kostova
May 2, 2002·Anti-cancer Drugs·Paul J Thornalley
Aug 29, 2007·Acta Pharmacologica Sinica·Yuesheng Zhang, Li Tang
Feb 24, 2001·Drug Metabolism and Drug Interactions·T J Smith, C S Yang
Apr 10, 2004·Drug Metabolism Reviews·Corwin HanschRajeshwar Prasad Verma
Jan 4, 2001·Drug Metabolism Reviews·S S Hecht
Jan 5, 2002·Expert Opinion on Investigational Drugs·T J Smith
Mar 8, 2005·Drug Metabolism Reviews·Shufeng ZhouYu-Zong Chen
Jan 10, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J VenhorstJ N M Commandeur
Apr 14, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Katarzyna SkupinskaTeresa Kasprzycka-Guttman
Sep 5, 2015·Bioorganic & Medicinal Chemistry Letters·Sarah M LewisKent S Gates
May 21, 2005·International Journal of Cancer. Journal International Du Cancer·Victoria YoxallCostas Ioannides
Feb 7, 2009·Environmental and Molecular Mutagenesis·Luca Valgimigli, Renato Iori
Feb 7, 2009·Environmental and Molecular Mutagenesis·Susan E Steck, James R Hebert
Feb 10, 2009·Journal of Biochemical and Molecular Toxicology·Katarzyna SkupinskaTeresa Kasprzycka-Guttman
Mar 31, 2007·Journal of Neurochemistry·Li KongWei Cao
Aug 29, 2014·Angewandte Chemie·Franziska S HanschenSascha Rohn
Sep 24, 2004·The International Journal of Biochemistry & Cell Biology·Peter RoseMatthew Whiteman
Jun 6, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·M La MarcaV Longo
Nov 9, 2017·International Journal of Molecular Sciences·János UrbancsokRalph Kissen

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