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（血小板激活因子，1-0-烷基-2(R)-(乙酰甘油基)-3-磷酸胆碱）引起血小板聚集、趋化性和多形核白细胞脱粒、平滑肌收缩、血管通透性和低血压。最近的研究表明，PAF可能与许多炎症、呼吸系统和心血管疾病有关。在我们从海洋生物中寻找新的PAF拮抗剂的项目中，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PAF的产生，这是由于A23817 和抑制 PAF 诱导的血小板聚集发现几种海绵代谢物如 manoalide、luffariolide A、bistheonllide A、 swinholide A、niphatesine A、hetonemin等均表现出PAF拮抗活性，IC_<50>值为0.05～5.0μg/mL。通过进一步研究这些化合物（萜类化合物）的构效关系，可能会发现更强大、更特异的PAF拮抗作用。 、生物碱等）如上所述。

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。”

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

Kobayashi, J.：“来自冲绳海生海绵 Hyrtios sp. 的具有 NGF 合成刺激活性的新型二元萜烯”。