METHODS AND RESULTS: All of these metabolites were phase I metabolites, with three new compounds including 2β-hydroxyl-Aeruginolactone (2), 14-hydroxyl-Aeruginolactone (3), 1β,8β-dihydroxyeudesm-4,7(11)-dien-8α,12-olide (4a), and four known compounds, 1β,10α,4α,5β-diepoxy-8α-hydroxy-glechoman-8α,12-olide (1), 1β,8β-dihydroxyeudesm-4(14),7(11)-dien-8α,12-olide (4b), 1β,8β-dihydroxyeudesm-3,7(11)-dien-8α,12-olide (5) and Aeruginolactone (6). Interestingly, the metabolite 6 was found to be a primary metabolite in urine, bile and feces. All metabolites were found to be both in urine and bile but only few metabolites except the metabolite 6 presented in feces after oral dose of furanodiene to rats. Furthermore, the metabolic pathways of furanodiene were proposed using an in vitro assay by incubation of furanodiene and its metabolites in vivo with rat liver S9 or liver microsomes.
CONCLUSIONS:
Clearly, Aeruginolactone (6) seemed to be a major precursor for other metabolites. |