Search for serine protease inhibitors from marine invertebrates.

点击翻译按钮获取中文摘要

Marine sponges (273 samples), coelenterates (32 samples), bryozoans (7 samples) and tunicates (26 samples) were collected from the Izu Peninsula, Hachijo Island, Kyushu and Shikoku. The hot methanol extracts of samples were partitioned between H_2O and CHCl_3 to give organic and aqueous layers. Each layer was assayed for inhibitory activities against thrombin and trypsin. Forty-five samples of sponges, 5 of coelenterates and 5 of tunicates were active. Genrally, activities were found in the aqueous layers, but some organic layers showed activities.One of active sponge sample, Theonella swinhoei was extracted, and the extract was fractionated to obtain a thrombin inhibitor named nazumamide A, which inhibited thrombin at an IC_<50> of 2.8 mug/mL. Amino acids analysis and spectral analyses including 2D NMR and FABMS led to a tetrapeptide possessing the N-2,5-dihydroxybenzoate terminus (1).Another active sponge Toxadocia cylindrica was similarly processed to yield a thrombin inhibitor, toxadocial A, which inhibited thrombin at an IC_<50> of 6.5 mug/mL. The structure elucidation was carried out by means of spectral analyses and chemical transformation to obtain an unusual tetrasulfated aldehyde as shown (2)