Search for PAF antagonits from marine organisms

从海洋生物中寻找 PAF 拮抗剂

• 批准号: 04453146
• 负责人: KOBAYASHI Jun'ichi
• 金额: $ 4.99万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04453146/
• 关键词: PAF antagonist; Sponge; Platelet aggregation; Marine organisms; Terpene; Alkaloid; PAF; マクロリド; テルペン; 活性成分; 海洋菌

PAF(platelet activating factor, 1-0-alkyl-2(R)-(acetylglyceryl)-3-phosphorylcholine) causea platelet aggregation, chemotaxis, and degranulation of polymorphonuclear leukocytes, smooth muscle contraction, m vascular permeability, and hyupotension. Recent studies have shown that PAF may be involved in many inflammator, respiratory, and cardiovascular diseases.In our project of search for new PAF autagonists from marine organisms, we systematically screened lipophilic extracts of Okinawan marine invertebrates and microorganisms for inhibition of PAF production due to A23817 and inhibition of PAF-induced platelet aggregation to find that several sponge metabolites such as manoalide, luffariolide A, bistheonllide A, swinholide A, niphatesine A, and heteronemin, exhibited PAF antagonistic activities with IC_<50> values of 0.05 - 5.0 mu g /mL.More powerful and specific PAF antagonistis may be fond through further studies of structure-activity relationship on the compounds (terpenes, alkaloid, etc.) described above.

PAF（血小板活化因子，1-O-烷基-2（R）-（乙酰甘油基）-3-磷酸胆碱）引起血小板聚集、趋化性、多形核白细胞的脱粒、平滑肌收缩、血管通透性和低血压。近年来的研究表明，PAF可能参与多种炎症、呼吸道和心血管疾病的发生，在我们从海洋生物中寻找新的PAF自体作用剂的项目中，我们系统地筛选了冲绳海洋无脊椎动物和微生物的亲脂性提取物，以抑制A23817引起的PAF产生和抑制PAF诱导的血小板聚集，发现几种海绵代谢产物如海松内酯、丝瓜络A、bistheonlide A、swinholide A、nipphatesine A和heteronemin等化合物具有PAF拮抗活性，IC值<50>为0.05 - 5.0 μ g /mL，通过进一步研究其构效关系，有望发现更强、更特异的PAF拮抗剂。上面描述

项目成果

M.Tsuda: "Luffariolides A-E, new sesterterpenes from the Okinawan marine sponge Luffariella sp." J.Org.Chem.57. 3503-3507 (1992)

M.Tsuda：“Luffariolides A-E，来自冲绳海绵 Luffariella sp. 的新二倍萜烯。”

J.Kobayashi: "Niphatesines E-H, new pyridine alkaloids from the Okinawan marine sponge Niphates sp." J.Chem.Soc.,Perkin Trans.1. 1291-1294 (1992)

J.Kobayashi：“Niphatesines E-H，来自冲绳海绵 Niphates sp 的新吡啶生物碱。”

J.Kobayashi: "New sesterterpenes with NGF-synthesis-stimulating activity from the Okinawan marine sponge Hyrtios sp." Chem.Pharm.Bull.41. 2190-2191 (1993)

J.Kobayashi：“来自冲绳海绵 Hyrtios sp 的具有 NGF 合成刺激活性的新型二倍萜烯。”

Kobayashi, J.: ""Luffariolides F and G, new manoalide congeners from the Okinawan marine sponge Luffariella sp."" J.Nat. Prod.56. 436-439 (1993)

Kobayashi, J.：“Luffariolides F 和 G，来自冲绳海洋海绵 Luffariella sp. 的新 manoalide 同系物。”J.Nat。

J.Kobayashi: "Luffariolides F and G,new manoalide congeners from the Okinawan marine sponge Luffariella sp." J.Nat.Prod.56. 436-439 (1993)

J.Kobayashi：“Luffariolides F 和 G，来自冲绳海绵 Luffariella sp. 的新 manoalide 同系物。”