In vitro metabolism of azasqualene derivatives and their effects on aminopyrine N-demethylase activity in rat liver microsomes.
The metabolism of squalene dimethylamine (I), a potent inhibitor of 2,3-oxidosqualene (SO) cyclase, and of sixteen other squalene derivatives was investigated in rat liver microsomes. N-oxidation was the only metabolic pathway observed, squalene dimethylamine N-oxide being the only metabolite isolated from incubation of I. The azasqualane and quaternary ammonium derivatives did not form N-oxides during their metabolism. The inhibition of aminopyrine N-demethylase activity was also studied and the IC50, for compound I, which shows weak competitive inhibition, was determined. At 1 mM concentration the other squalene derivatives showed a range of inhibition activity possibly due to their different lipophilicity.
Viola
F
F
Istituto di Chimica Farmaceutica Applicata, Università di Torino, Italy.
Grosa
G
G
Ceruti
M
M
Caputo
O
O
Cattel
L
L
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001372:Aza Compounds / Q000378:metabolism* / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013185:Squalene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D001372:Aza Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D013185:Squalene; D000633:Aminopyrine N-Demethylase