Deacylation of N-Arylformamides andN-Arylacetamides by Formamidase in Rat Liver

Abstract

ABSTRACT:The in vitro deacylation of N-arylformamides and N-arylacetamides to arylamines was examined in rat liver preparations. When 2-acetylaminofluorene or 2-formylaminofluorene was incubated with rat liver microsomes or cytosol, the deacylated metabolite, 2-aminofluorene, was formed. The deacylating activity of liver microsomes was inhibited by bis(4-nitrophenyl)phosphate and phenylmethanesulfonyl fluoride, inhibitors of carboxylesterase. In contrast, the activity of liver cytosol was inhibited by diisopropyl fluorophosphate, an inhibitor of formamidase.Deacylation of these compounds appear to be mainly catalyzed by carboxylesterase in liver microsomes and formamidase in liver cytosol. 2-Formylaminofluorene, 2-acetylaminofluorene, 1-formylaminopyrene, 4-formylaminobiphenyl, 2-formylaminonaphthalene, 1-formylaminonaphthalene, and 2-acetylaminofluorene were deacylated by formamidase purified from rat liver cytosol. Formamidase catalyzed both Nformylation of arylamines, and deacylation of N-arylformamides and N-arylacetamides.

Metabolic Fate of the Isocyanide Moiety: Are Isocyanides Pharmacophore Groups Neglected by Medicinal Chemists?

“…Finally, at least for aryl isocyanide 1 , we demonstrated that formamidine 1NG spontaneously degrades to formamide 1FA . It was previously established that in mammalian liver, N -arylamines can undergo N -acetylation/formylation; on the contrary, the corresponding N -aryl formamides are deformylated in liver cytosol by formamidases, and, to a lesser extent, in microsomes, where carboxylesterases are supposed to play a role …”

Deacylation of N-Formylanilines and N-Acetylanilines by Rat Liver Formamidase

“…8) Recently, we reported that 2-formylaminofluorene was deformylated to 2-aminofluorene by rat liver formamidase. 24) In this study, we have demonstrated that formamidase also catalyzes the deacylation of N-formylanilines and N-acetylanilines to aniline derivatives, in addition to the N-formylation of anilines to N-formylanilines. Santti and Hopsu-Havu 25) reported that formamidase catalyzed the hydrolysis of formyl-1-aminonaphthalene.…”