Identification of three new n-demethylated and o-demethyled bisbenzylisoquinoline alkaloid metabolites of isoliensinine from dog hepatic microsomes

Abstract

Isoliensinine, a natural phenolic bisbenzyltetrahydroisoquinoline alkaloid, has received considerable attention for its potential biological effects such as antioxidant and anti-HIV activities. From the dog hepatic microsomes of isoliensinine, three new N-demethylated and O-demethylated metabolites, 2-N-desmethyl-isoliensinine (M1), 2'-N-desmethylisoliensinine (M2), and 2'-N-6-O-didesmethylisoliensinine (M3), were identified by high-performance liquid chromatography and data-dependent electrospray ionization tandem mass spectrometry. Possible metabolic pathways for isoliensinine have been proposed. The result should prove very helpful for evaluation of the drug-like properties of isoliensinine and other bisbenzylisoquinoline alkaloids. © 2012 by the authors; licensee MDPI, Basel, Switzerland.