Rat liver microsomal ring- and S-oxidation of thiaarenes with central or peripheral thiophene rings

Abstract

The metabolism of the following thiaarenes has been investigated using liver microsomes of untreated, phenobarbital-, Aroclor R- and 5,6-benzoflavone-pretreated rats: dibenzothiophene, naphtho[2,1- b]thiophene, benzo[ b]naphtho[2,1- b]thiophene, benzo[ b]naphtho[1,2- d]thiophene, benzo[ b]naphtho-[2,3- d]thiophene, phenanthro[1,2- b]thiophene, phenanthro[4,5- bcd] thiophene, triphenyleno[1,12- bcd]-thiophene and dinaphtho[2,1- b:1′,2′- d]thiophene. Thiaarenes with a central thiophene ring preferentially undergo S-oxidation and are converted into sulfoxides and sulfones, whereas those with a peripheral thiophene ring are oxidized at the carbocyclic skeleton resulting in the formation of phenols, dihydrodiols and triols. Sulfone formation seems to be inducible by phenobarbital but only little or not by 5,6-benzoflavone treatment. In most cases 5,6-benzoflavone and Aroclor R treatment enhanced the rates of ring oxidation.