Comparison of the Biological Properties of Several Marine Sponge-Derived Sesquiterpenoid Quinones

Abstract

Eight naturally occurring marine-sponge derived sesquiterpenoid quinones wereevaluated as potential inhibitors of pyruvate phosphate dikinase (PPDK), a C₄ plantregulatory enzyme. Of these, the hydroxyquinones ilimaquinone, ethylsmenoquinone andsmenoquinone inhibited PPDK activity with IC₅₀’s (reported with 95% confidenceintervals) of 285.4 (256.4 – 317.7), 316.2 (279.2 – 358.1) and 556.0 (505.9 – 611.0) μM,respectively, as well as being phytotoxic to the C₄ plant Digitaria ciliaris. The potentialanti-inflammatory activity of these compounds, using bee venom phospholipase A₂(PLA₂), was also evaluated. Ethylsmenoquinone, smenospongiarine, smenospongidine andilimaquinone inhibited PLA₂ activity (% inhibition of 73.2 + 4.8 at 269 μM, 61.5 + 6.1 at242 μM, 41.0 + 0.6 at 224 μM and 36.4 + 8.2 at 279 μM, respectively). SAR analysesindicate that a hydroxyquinone functionality and a short, hydroxide/alkoxide side-chain atC-20 is preferred for inhibition of PPDK activity, and that a larger amine side-chain at C-20 is tolerated for PLA₂ inhibitory activity.