Comparative effect of chemical structure of chlorinated N-hydroxy-N-acyl-aminobiphenyl ethers and their related compounds on rat liver cytosol-catalyzed transacylation.

Studies of structure-transacylation relationships for a series of acylhydroxamic acids of chlorinated biphenyl ethers and their related compounds by rat liver N-arylacylhydroxamic acid-dependent N-acyltransferase (AHNAT) are described. In the transacylation of 4-aminoazobenzene catalyzed by AHNAT, 4-substituents (chloro, phenoxy, and mono-, di-, and trichlorophenoxy groups) of N-phenylacetohydroxamic acid enhanced the ability of the unsubstituted hydroxamic acid to serve as acetyl donors. As to the number of chlorines in the phenoxy group, the activity increased with decreasing number from three to zero. Of the monochlorophenoxy compounds, the 4'-chloro compound was the most effective acetyl donor. In 3-substituents (chloro and phenoxy groups) of N-phenylacetohydroxamic acid, the 3-chloro compound was an effective acetyl donor similarly to the 4-chloro compound, whereas the 3-phenoxy compound was 48% as active as the 4-phenoxy compound. None of 2-substituted N-phenylacetohydroxamic acids examined showed transacetylation activity. As to the effect of acyl group structure on the activity, N-propionyl, N-glycoloyl, and N-formyl derivatives of the 4-(4'-chlorophenoxy) compound were only 4, 2, and 0% as active as the corresponding acetyl compound, respectively. Esterification of the N-arylacetohydroxamic acid decreased the activity; O-acetyl, O-methyl, O-glucosyl, and O-glucuronosyl derivatives of the 4-(4'-chlorophenoxy) compound were 35, 7, 0, and 0% as active as the corresponding N-hydroxy compound, respectively.