Development of anti-allergics against antianaphylaxis type by lead-optimization

从小叶厚皮藤中分离得到的小叶厚皮藤酮（Microphyllone，Microphyllone）在~ □M浓度下对RBL-2 H3细胞的胞吐有抑制作用。本文对一种新型抗过敏化合物小叶酮的理化性质和生物学特性进行了研究。小叶绿酮不仅能抑制RBL-2 H3细胞的胞吐作用，而且能抑制大鼠肥大细胞和人嗜碱性粒细胞的胞吐作用。小叶绿酮抑制刺激引起的细胞内钙离子浓度的增加，这是由于抑制了通过钙释放激活的钙通道（CRAC）的钙内流。此外，我们还确定了在以下过敏模型中的小叶章酮的作用。小叶绿酮抑制被动皮肤过敏反应和蛔虫引起的双相皮肤过敏反应的即刻相。另一方面，叶绿酮对IV型变态反应模式如蛔虫诱导的双相皮肤变态反应晚期和恶唑酮诱导的接触型迟发性皮肤反应无影响。小叶绿酮有望成为一种新型的抗过敏药物和/或新型抗过敏药物的先导化合物。

Microphyllone isolated from Ehretia microphylla has the inhibitory activity on exocytosis in RBL-2H3 cells at _□M concentration. We have determined the physicochemical and biological characters of microphyllone as a novel anti-allergic compound. Microphyllone inhibited exocytosis not only in RBL-2H3 cells but also in rat mast cells, and human basophiles with various stimuli. Microphyllone inhibited an increase in concentration of intracellular calcium ion by stimulation, which is due to inhibition of calcium influx through calcium release-activated calcium (CRAC) channel. We, furthermore, determine the effects of microphyllone in the following allergic models. Microphyllone suppressed passive cutaneous anaphylaxis reaction and immediate phase of ascaris-induced biphasic skin allergic reaction. On the other hand, microphyllone has no effect on type-IV allergic modes such as late phase of ascaris-induced biphasic skin allergic reaction and oxazolone-induced contact type delayed cutaneous reaction. Microphyllone can be a new type of anti-allergics and/or a lead compound for new class anti-allergics against acute allergic reactions.