Comparison of the biological properties of several marine sponge-derived sesquiterpenoid quinones

Eight naturally occurring marine-sponge derived sesquiterpenoid quinones were evaluated as potential inhibitors of pyruvate phosphate dikinase (PPDK), a C-4 Plant regulatory enzyme. Of these, the hydroxyquinones ilimaquinone, ethylsmenoquinone and smenoquinone inhibited PPDK activity with IC50's (reported with 95% confidence intervals) of 285.4 (256.4 - 317.7), 316.2 (279.2 - 358.1) and 556.0 (505.9 - 611.0) gm, respectively, as well as being phytotoxic to the C4 plant Digitaria ciliaris. The potential anti-inflammatory activity of these compounds, using bee venom phospholipase A(2) (PLA(2)), was also evaluated. Ethylsmenoquinone, smenospongiarine, smenospongidine and ilimaquinone inhibited PLA2 activity (% inhibition of 73.2 +/- 4.8 at 269 mu M, 61.5 +/- 6.1 at 242 mu M, 41.0 +/- 0.6 at 224 mu M and 36.4 +/- 8.2 at 279 mu M, respectively). SAR analyses indicate that a hydroxyquinone functionality and a short, hydroxide/alkoxide side-chain at C-20 is preferred for inhibition of PPDK activity, and that a larger amine side-chain at C20 is tolerated for PLA(2) inhibitory activity.