Search for the New Biological Response Modifiers Targeting on TNFα from the Marine Invertebrates

从冲绳软珊瑚（Sinularia sp.）中鉴定出两种去骨皮质二萜，去骨皮质烯内酯和去骨皮质烯内酯，它们对lps诱导的RAW 264细胞产生TNFα有明显的抑制作用。^<1)>从冲绳软珊瑚（Sinularia flexibilis）中鉴定出一种膜二萜，柔韧素（= sinularine），它对L929细胞的TNFα有明显的抑制作用。从海绵（Amphimedon sp.）中分离到5种新的鞘糖脂，它们对RAW 264细胞产生TNFα有促进作用。TNFα是众所周知的调节血管生成的物质。从苔藓虫（Watersipora subtorquata d' Orbigny, 1852）中分离到一种新的蒽醌——苔藓蒽噻吩，它对BAE细胞具有最有效的抗血管生成活性。^<3) bb0从冲绳海绵（Amphimedon paraviridis）中鉴定出一种抗血管生成嘌呤类似物1,3-二甲基异胍。TNFα是有效的死亡因子之一。从海绵体中分离到一种新的非甾体甾醇，发现其可诱导人急性早幼粒细胞白血病细胞凋亡。在本项目期间，从海绵（Ircinia sp.）中分离到一种新的多药耐药调节剂Ircinia磺酸。^<5)>从海绵（Axinyssa sp.）中分离到一种新的细胞毒性二萜(-)- Axinyssa sp.)

Two norcembrane diterpenes, norcembrenolide and sinuleptolide were identified from the Okinawan soft coral (Sinularia sp.), and they demonstrated a potent inhibitory effect on LPS-induced TNFα production by RAW 264 cells.^<1)> A cembrane diterpene, flexibilide (= sinularine) was identified from the Okinawan soft coral (Sinularia flexibilis), and it demonstrated a potent inhibitory effect on TNFα by L929 cells. Five new glycosphingolipids were isolated from the marine sponge (Amphimedon sp.), and they demonstrated a promoting effect on TNFα production by RAW 264 cells.TNFα is well known substance to modulate the angiogenesis. A new anthraquine, bryoanthrathiophene was isolated from the bryozoan (Watersipora subtorquata d' Orbigny, 1852), and it demonstrated the most potent antiangiogenic activity on BAE cells.^<3)> An antiangiogenic purine analog, 1,3-dimethylisoguaninium was identified from the Okinawan marine sponge (Amphimedon paraviridis).^<6)>TNFα is one of the potent death-factors. A new abeo-sterol, orostanal was isolated form the marine sponge (Stelletta hiwasaensis), and orostanal and its synthetic analog induce apoptosis in human acute promyelotic leukemia cells.^<4)>During the term of this project, a new multidrug resistance modulator, irciniasulfonic acid was isolated from the marine sponge (Ircinia sp.).^<5)> A new cytotoxic diterpene, (-)-axinyssene was isolated from the marine sponge (Axinyssa sp.).^<2)>