Bioactive pyridoacridine alkaloids from the micronesian sponge Oceanapia sp.
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.
Eder
C
C
Julius-von-Sachs-Institut für Biowissenschaften, Lehrstuhl für Pharmazeutische Biologie, Würzburg, Germany.
Schupp
P
P
Proksch
P
P
Wray
V
V
Steube
K
K
Müller
C E
CE
Frobenius
W
W
Herderich
M
M
van Soest
R W
RW
D000166:Acridines / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D000470:Alkaloids / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D001156:Artemia; D001419:Bacteria / Q000187:drug effects; D002963:Cladosporium / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism
D000166:Acridines; D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D007306:Insecticides; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1