Anti-fertilization activity of a spirocyclic sesquiterpene isocyanide isolated from the marine sponge Geodia exigua and related compounds.
(-)-10-epi-Axisonitrile-3, a spirocyclic sesquiterpene isocyanide obtained from the marine sponge Geodia exigua, immobilized sperm of sea urchin and starfish to block fertilization at the minimum effective concentration of 0.4 microg/ml. On the other hand, fertilized eggs developed normally to the gastrula stage in the presence of a 250-times higher concentration of the isocyanide. Analysis by (31)P NMR revealed an accumulation of phosphocreatine and a depletion of inorganic phosphate in the isocyanide-treated sperm, suggesting that (-)-10-epi-axisonitrile-3 inhibited the phosphocreatine shuttle participating in the high-energy phosphate metabolism, thereby immobilizing sperm to block fertilization. No analogs of (-)-10-epi-axisonitrile-3 containing different functionalities or isocyanides with different carbon skeleton exhibited such activity.
Ohta
Emi
E
Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.
Uy
Mylene M
MM
Ohta
Shinji
S
Yanai
Mihoko
M
Hirata
Toshifumi
T
Ikegami
Susumu
S
D000818:Animals; D003486:Cyanides / Q000138:chemical synthesis / Q000494:pharmacology*; D004447:Echinodermata; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005306:Fertilization / Q000187:drug effects*; D005854:Germ Cells / Q000187:drug effects; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010725:Phosphocreatine / Q000037:antagonists & inhibitors; D011161:Porifera; D012717:Sesquiterpenes; D013094:Spermatozoa / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015053:Zygote / Q000187:drug effects
D003486:Cyanides; D009570:Nitriles; D012717:Sesquiterpenes; D013141:Spiro Compounds; D010725:Phosphocreatine; C424432:axisonitrile 3