The Imidazoacridinone Antitumor Drug, C-1311, Is Metabolized by Flavin Monooxygenases but Not by Cytochrome P450s

5-Diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) is an antitumor agent that is also active against autoimmune diseases. The intention of the present studieswas to elucidate the role of selected liver enzymes in metabolism of C-1311 and the less active 8-methyl deriva-tive, 5-diethylaminoethylamino-8-methoxyimidazoacridinone (C-1330). Compoundswere incubatedwith rat livermicrosomal fraction,with a set of 16 human liver protein samples, and with human recombinant isoen-zymes of cytochrome P450, flavin monooxygenases (FMO), and UDP-glucuronosyltransferase (UGT). Our results showed that C-1311 and C-1330weremetabolizedwith human livermicrosomal enzymesbut not with any tested human recombinant cytochromes P450 (P450s). Two of these, CYP1A2 and CYP3A4, were inhibited by both compounds. In addition, results of C-1311 elimination fromhepatic reductase-null mice, in which liver NADPH-P450 oxidoreductase has been deleted indicated that liver P450s were slightly engaged in drug transformation. In con