BIOACTIVE PYRIDOACRIDINE ALKALOIDS FROM THE MICRONESIAN SPONGE OCEANAPIA SP

The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alk aloids: the known compounds kuanoniamine C (1) and kuanoniamine D (2), as well as the new N-deacyl derivative (3) of the kuanoniamines. Comp ounds 1 and 2 exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (LC50 of 156 and 59 ppm, respectively), when incorporated into artificial diet. Both comp ounds also showed toxicity in the brine shrimp lethality test with a L C50 of 37 mu g/mL (compound 1) and 19 mu g/mL (compound 2), respective ly. 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 (3) appeared to be active in the same range of concentrations as kuanoniamine C (1) and D (2). The IC50 of 3 was 1.2 mu g/mL toward HeLa cells and 2.0 mu g/mL toward MON O-MAC 6 cells. In receptor binding assays compound 2 showed affinity t o A(1)- and A(2A)-adenosine receptors with K-i values of 2.94 and 13.7 mu M, respectively. Compound 1 was less active than compound 2, where as compound 3 showed no affinity toward adenosine receptors. In additi on, compounds 1-3 exhibited moderate affinity to benzodiazepine bindin g sites of GABA(A) receptors.