Spongiapyridine and Related Spongians Isolated from an Indonesian <i>Spongia</i> sp.

Abstract

New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (<b>1</b>), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (<b>2</b>), and spongiapyridine (<b>3</b>) and the known compound 17-hydroxy-4-<i>epi</i>-spongialactone A (<b>4</b>) were isolated from an Indonesian sponge of the genus <i>Spongia</i>. The structures of <b>1</b>–<b>3</b> were deduced by analyses of physical and spectroscopic data. Diterpene <b>3</b> 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-<i>d</i>₄. 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 <b>2</b> 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