STRUCTURAL RELATIONSHIP OF EPIPOLYTHIODIOXOPIPERAZINES AND THEIR IMMUNOMODULATING ACTIVITY
STRUCTURAL RELATIONSHIP OF EPIPOLYTHIODIOXOPIPERAZINES AND THEIR IMMUNOMODULATING ACTIVITY
复制标题
DOI：
10.1016/0161-5890(86)90047-7
复制
发表时间：
1986-02-01
影响因子：
3.6
通讯作者：
EICHNER, RD
中科院分区：
文献类型：
--
作者：
MULLBACHER, A;WARING, P;EICHNER, RD
在体外测试表聚硫代二氧代哌嗪的免疫调节活性。使用巨噬细胞粘附试验作为抑制吞噬作用的量度，它们对混合淋巴细胞培养物中的刺激细胞的作用和它们抑制T淋巴细胞的促分裂原刺激的能力，观察到活性的层次，其中孢子溶素是最活跃的，其次是胶毒素和1，4-二甲基-3，6-表二硫代-2，5-二氧代哌嗪。胶毒毒素的衍生物，如硫代胶毒毒素、三硫化物胶毒毒素和四硫化物胶毒毒素具有与胶毒毒素相当的活性。胶霉毒素的二甲基硫醚衍生物没有活性。还原剂的存在消除epipolithiodioxopiperazines的活性。这表明桥连的二硫化物部分是其活性的单一最重要的化学实体。活性化合物的不同活性可归因于它们的亲脂性的变化。
Epipolythiodioxopiperazines were tested for their immunoregulatory activity in vitro. Using the macrophage adherence test as a measure of inhibition of phagocytosis, their effect on stimulator cells in mixed lymphocyte cultues and their ability to inhibit mitogen stimulation of T lymphocytes, a hierarchy of activity was observed, with sporidesmin being the most active, followed by gliotoxin and 1,4-dimethyl-3,6-epidithio-2,5-dioxopiperazine. Derivatives of gliotoxin such as dehydro-, trisulfide and tetrasulfide gliotoxin have activities comparable to gliotoxin. The dimethylthioether derivative of gliotoxin was devoid of activity. The presence of reducing agents abrogated the activity of epipolythiodioxopiperazines. This suggests that the bridged disulide moiety is the single most important chemical entity for their activity. The differential activities of the active compounds may be attributable to their variations in lipophilic properties.