Eder C, Schupp P, Proksch P, Wray V, Steube K, Müller C E, Frobenius W, Herderich M, van Soest R W
Julius-von-Sachs-Institut für Biowissenschaften, Lehrstuhl für Pharmazeutische Biologie, Würzburg, Germany.
J Nat Prod. 1998 Feb;61(2):301-5. doi: 10.1021/np9702704.
The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alkaloids: the known compounds kuanoniamine C (1) and kuanoniamine D (2), as well as the new N-deacyl derivative (3) of the kuanoniamines. Compounds 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 compounds also showed toxicity in the brine shrimp lethality test with a LC50 of 37 micrograms/mL (compound 1) and 19 micrograms/mL (compound 2), respectively. The N-deacyl derivative did not show any remarkable effect in both bioassays. Cytotoxcity 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 micrograms/mL toward HeLa cells and 2.0 micrograms/mL toward MONO-MAC 6 cells. In receptor binding assays compound 2 showed affinity to A1- and A2A-adenosine receptors with Ki values of 2.94 and 13.7 microM, respectively. Compound 1 was less active than compound 2, whereas compound 3 showed no affinity toward adenosine receptors. In addition, compounds 1-3 exhibited moderate affinity to benzodiazepine binding sites of GABAA receptors.
密克罗尼西亚海绵 Oceanapia sp. 产生了三种吡啶并吖啶生物碱：已知化合物宽诺胺 C（1）和宽诺胺 D（2），以及宽诺胺的新 N-脱酰基衍生物（3）。当将化合物 1 和 2 掺入人工饲料中时，它们对多食性害虫斜纹夜蛾的新生幼虫表现出杀虫活性（LC50 分别为 156 和 59 ppm）。这两种化合物在卤虫致死试验中也显示出毒性，LC50 分别为 37 微克/毫升（化合物 1）和 19 微克/毫升（化合物 2）。N-脱酰基衍生物在这两种生物测定中均未显示出任何显著效果。使用两种人类细胞系在体外研究了这些生物碱的细胞毒性。新衍生物（3）在与宽诺胺 C（1）和 D（2）相同的浓度范围内似乎具有活性。化合物 3 对 HeLa 细胞的 IC50 为 1.2 微克/毫升，对 MONO-MAC 6 细胞的 IC50 为 2.0 微克/毫升。在受体结合试验中，化合物 2 对 A1 和 A2A 腺苷受体表现出亲和力，Ki 值分别为 2.94 和 13.7 microM。化合物 1 的活性低于化合物 2，而化合物 3 对腺苷受体没有亲和力。此外，化合物 1-3 对 GABAA 受体的苯二氮䓬结合位点表现出中等亲和力。
