Bioactive Pyridoacridine Alkaloids from the Micronesian Sponge Oceanapia sp.

The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alkaloids:  the known compounds kuanoniamine C (<BO>1</BO>) and kuanoniamine D (<BO>2</BO>), as well as the new N-deacyl derivative (<BO>3</BO>) of the kuanoniamines. Compounds <BO>1</BO> and <BO>2</BO> exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (LC<INF>50</INF> of 156 and 59 ppm, respectively), when incorporated into artificial diet. Both compounds also showed toxicity in the brine shrimp lethality test with a LC<INF>50</INF> of 37 μg/mL (compound <BO>1</BO>) and 19 μg/mL (compound <BO>2</BO>), respectively. The N-deacyl derivative did not show any remarkable effect in both bioassays. Cytotoxicity of the alkaloids was studied in vitro, using two human cell lines. The new derivative (<BO>3</BO>) appeared to be active in the same range of concentrations as kuanoniamine C (<BO>1</BO>) and D (<BO>2</BO>). The IC<INF>50</INF> of <BO>3</BO> was 1.2 μg/mL toward HeLa cells and 2.0 μg/mL toward MONO-MAC 6 cells. In receptor binding assays compound <BO>2</BO> showed affinity to A<INF>1</INF>- and A<INF>2A</INF>-adenosine receptors with K<INF>i</INF> values of 2.94 and 13.7 μM, respectively. Compound <BO>1</BO> was less active than compound <BO>2</BO>, whereas compound <BO>3</BO> showed no affinity toward adenosine receptors. In addition, compounds <BO>1</BO>−<BO>3</BO> exhibited moderate affinity to benzodiazepine binding sites of GABA<INF>A</INF> receptors.