Spongiapyridineand Related Spongians Isolated froman Indonesian Spongia sp.

摘要

New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (>1), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (>2), and spongiapyridine (>3) and the known compound 17-hydroxy-4-epi-spongialactone A (>4) were isolated from an Indonesian sponge of the genus Spongia. The structures of >1–>3 were deduced by analyses of physical and spectroscopic data. Diterpene >3 is unusual, as the D-ring is a pyridyl ring system rather than the standard δ-lactone. The structure elucidation of this compound was complicated by facile exchange of the axial proton at the C-11 methylene with deuterium from methanol-d4. The isolated compounds were tested for biological activity in a battery of in vitro assays (TNF-α-induced NFκB, LPS-induced iNOS, RXR stimulation, quinone reductase 1 induction, aromatase inhibition, TRPM7 ion channels, and aspartic protease BACE1 inhibition). Norditerpene >2 modestly inhibited aromatase with an IC50 of 34 μM and induced quinone reductase 1 activity with a CD (the concentration needed to double the enzymatic response) of 11.2 μM. The remaining isolates were inactive.