Hayashi M, Kim Y P, Takamatsu S, Enomoto A, Shinose M, Takahashi Y, Tanaka H, Komiyama K, Omura S
Kitasato Institute, Kitasato University, Tokyo, Japan.
J Antibiot (Tokyo). 1996 Nov;49(11):1091-5. doi: 10.7164/antibiotics.49.1091.
Selective growth inhibition against IL-6-dependent cells was detected in fermentation extracts of a microbial strain, K93-0711, which was characterized as Streptomyces species. Active metabolite, termed madindoline A and B, were isolated, and the structure was determined to be 3a-hydroxy-indoline with diketocyclopentene at the N position. Madindoline A and B displayed dose-dependent inhibition of MH60 cells, an IL-6-dependent cell line, in presence of 0.1 U/ml IL-6. The IC50 for madindoline A and B against this cell line was 8 microM and 30 microM, respectively. These compounds did not inhibit the growth of cell lines which are not IL-6 dependent and the growth inhibition of the MH60 cell line was reversed by addition of excess, 0.4 U/ml, of IL-6 to the culture media. These compounds did not show any antimicrobial activity at a concentration of 1,000 micrograms/ml.
在一株被鉴定为链霉菌属的微生物菌株K93 - 0711的发酵提取物中，检测到了对白细胞介素-6（IL - 6）依赖细胞的选择性生长抑制作用。分离出了名为马吲哚啉A和B的活性代谢产物，其结构被确定为在N位带有二酮环戊烯的3a - 羟基吲哚啉。在存在0.1 U/ml IL - 6的情况下，马吲哚啉A和B对MH60细胞（一种IL - 6依赖细胞系）表现出剂量依赖性抑制作用。马吲哚啉A和B对该细胞系的半数抑制浓度（IC50）分别为8微摩尔和30微摩尔。这些化合物不抑制非IL - 6依赖的细胞系的生长，并且通过向培养基中添加过量的（0.4 U/ml）IL - 6可逆转对MH60细胞系的生长抑制作用。在浓度为1000微克/毫升时，这些化合物未显示出任何抗菌活性。
