Spongiapyridine and Related Spongians Isolated from an Indonesian Spongia sp.

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 delta-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-d(4) The isolated compounds were tested for biological activity in a battery of in vitro assays (TNF-alpha-induced NF kappa B, 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 mu M and induced quinone reductase 1 activity with a CD (the concentration needed to double the enzymatic response) of 11.2 mu M. The remaining isolates were inactive.