Anti-angiogenic activities of gliotoxin and its methylthio-derivative, fungal metabolites
Anti-angiogenic activities of gliotoxin and its methylthio-derivative, fungal metabolites
复制标题
DOI：
10.1007/bf02975182
复制
发表时间：
2001-10-01
影响因子：
6.7
通讯作者：
Lee, JJ
中科院分区：
文献类型：
--
作者：
Lee, HJ;Lee, JH;Lee, JJ
在寻找新的天然血管生成抑制剂的过程中，我们发现两种未知真菌菌株的培养液对体外人脐静脉内皮细胞（HUVEC）的毛细血管样管形成具有有效的抑制活性。通过生物测定引导分离分离出两种活性化合物，并通过光谱分析将其结构鉴定为胶霉毒素 (1) 及其衍生物甲基硫胶毒素 (2)。通过体外创伤迁移测定评估，这些化合物显着抑制 HUVEC 的迁移，并且与 HeLa、MCF-7 和 KB 3-1 细胞等癌细胞系相比，对 HUVEC 增殖的抑制作用至少强 10 倍。特别是，具有二硫基团的胶霉毒素比甲硫胶霉毒素发挥更有效的活性，这表明胶霉毒素可能是作为抗血管生成剂进行进一步研究的有用化合物。
In the search for new naturally occurring angiogenic inhibitor, we found that culture broths from two unidentified fungal strains exerted potent inhibitory activities on capillary-like tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Two active compounds were isolated by bioassay-guided separation and their structures were identified as gliotoxin (1) and its derivative methylthiogliotoxin (2) by spectroscopic analyses. These compounds significantly inhibited the migration of HUVEC assessed by in vitro wounding migration assay and exhibited at least 10 times more potent inhibition of proliferation of HUVECs as compared with that of cancer cell lines such as HeLa, MCF-7, and KB 3-1 cells. Especially, gliotoxin having disulfide group exerted more potent activities than methylthiogliotoxin, suggesting that gliotoxin could be a useful compound for further study as an anti-angiogenic agent.