Microsomal metabolism of dictamnine: identification of metabolites and evaluation of their mutagenicity in Salmonella typhimurium

Incubation of the furoquinoline alkaloid dictamnine with microsomal fractions from phenobarbital-induced rat liver resulted in a metabolite mixture from which demethyl-dictamnine and dictamnic acid were identified by a GCMS technique. The identity of the two compounds was confirmed by synthesis. Other metabolites were characterized by their mass spectra only. The pattern of the metabolites suggested a possible pathway of metabolism in vitro. We assume that the metabolism of dictamnine is analogous to the metabolism of the related 8-methoxypsoralen and takes place via an unstable epoxide and subsequent oxidative opening of the furan ring. Direct evidence for the formation of an epoxide was, however, not obtained. The identified compounds as well as some putative metabolites were shown to be non-mutagenic in Salmonella typhimurium TA98 except for 8-hydroxydictamnine, which, however, was not detected in the metabolite mixture.