Sakai Ryuichi, Matsubara Hiroki, Shimamoto Keiko, Jimbo Mituru, Kamiya Hisao, Namikoshi Michio
Kitasato University School of Fisheries Sciences, Sanriku-cho, Ofunato, Iwate 022-0101 Japan.
J Nat Prod. 2003 Jun;66(6):784-7. doi: 10.1021/np020590+.
The bioassay-guided fractionation of the water-soluble extract of the marine sponge Cribrochalina olemda collected in Palau resulted in the isolation of a new amino acid cribronic acid (1): (2S,4R,5R)-5-hydroxy-4-sulfooxypiperidine-2-carboxylic acid. However, aqueous extracts of Stylotella aurantium and Axinella carteri collected in Yap State, Micronesia, afforded a known N-methyl-d-aspartic acid (NMDA)-type glutamate receptor agonist, (2S,4S)-4-sulfooxypiperidine-2-carboxylic acid (2), as a common active principle. Both 1 and 2 induced convulsive behaviors in mice upon intracerebroventricular (icv) injection with ED(50) values of 29 +/- 3.0 and 20 +/- 2.8 pmol/mouse, respectively. Radioligand binding assay using rat cerebrocortical membrane demonstrated that 1 and 2 inhibit the binding of the labeled NMDA receptor ligand [(3)H]CGP39653 at IC(50) values of 83 +/- 15 and 214 +/- 20 nM, respectively. However, 1 and 2 did not displace [(3)H]kainic acid or [(3)H]AMPA. These data indicated that 1 is a selective NMDA-type glutamate receptor ligand with potent convulsant activity in mice.
对在帕劳采集的海洋海绵奥氏筛网海绵水溶性提取物进行生物测定指导下的分级分离，得到了一种新的氨基酸筛网氨酸（1）：（2S，4R，5R）-5-羟基-4-磺氧基哌啶-2-羧酸。然而，在密克罗尼西亚雅浦州采集的金色笔海绵和卡特里斧海绵的水提取物，得到了一种已知的N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体激动剂，（2S，4S）-4-磺氧基哌啶-2-羧酸（2），作为共同的活性成分。1和2经脑室内（icv）注射后均能在小鼠中诱导惊厥行为，ED（50）值分别为29±3.0和20±2.8 pmol/小鼠。使用大鼠大脑皮层膜进行的放射性配体结合试验表明，1和2分别以83±15和214±20 nM的IC（50）值抑制标记的NMDA受体配体[（3）H]CGP39653的结合。然而，1和2不能取代[（3）H]海人酸或[（3）H]AMPA。这些数据表明，1是一种选择性的NMDA型谷氨酸受体配体，在小鼠中具有强大的惊厥活性。
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