(E)-2-Benzylidenecyclanones: Part XVII. An LC-MS study of microsomal transformation reactions of (E)-2-[(4'-methoxyphenyl)methylene]-benzosuberon-1-one: A cyclic chalcone analog

Abstract

Biotransformation of the antiproliferative (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-one (2c) was studied using rat liver microsomes. As a result of the CYP-catalyzed transformations, one monooxygenated (2c+O) and the demethylated (2c-CH2) metabolites were identified by HPLC-MS. (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-ol, the expected product of rat liver microsomal carbonyl reductase, was not found in the incubates. Microsomal GST-catalyzed reaction of the compound resulted in formation of diastereomeric GST-conjugates. Under the present HPLC conditions, the diastereomeric adducts were separated into two chromatographic peaks (2c-GSH-1 and 2c-GSH-2).