Inhibition of rat hepatic aryl sulphotransferase IV by dihydrodiol derivatives of benzo[a]pyrene and naphthalene.
1. Although neither the (+)- nor (-)-enantiomer of trans-benzo[a]pyrene-7,8-dihydrodiol was a substrate for aryl sulphotransferase IV from rat liver, both enantiomers inhibited the enzyme-catalysed sulphation of 1-naphthalene-methanol with Ki values of 3.7 +/- 0.4 microM for the (+)-enantiomer, and 4.4 +/- 0.3 microM for the (-)-enantiomer. 2. Based on the magnitude of the Ki values, the binding affinity of these dihydrodiols for the aryl sulphotransferase was significantly greater than that for the corresponding phenolic derivatives of benzo[a]pyrene. That is 7-hydroxybenzo[a]pyrene and 8-hydroxybenzo[a]pyrene were both substrates for aryl sulphotransferase IV, with apparent Km values of 280 +/- 41 microM and 370 +/- 72 microM, respectively. 3. Both (+)- and (-)-trans-naphthalene-1,2-dihydrodiols were also inhibitors of aryl sulphotransferase IV, but with higher Ki values than would be expected from previously determined apparent Km and Ki values for (R)-(-)- and (S)-(+)-1,2,3,4-tetrahydro-1-naphthols, respectively.
Rao
S I
SI
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Duffel
M W
MW
D000818:Animals; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D004101:Dihydroxydihydrobenzopyrenes; D009281:Naphthalenes; D015239:Arylsulfotransferase