Ichimura M, Ogawa T, Katsumata S, Takahashi K, Takahashi I, Nakano H
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
J Antibiot (Tokyo). 1991 Oct;44(10):1045-53. doi: 10.7164/antibiotics.44.1045.
Six duocarmycins have been discovered during our search for new antitumor antibiotics and they showed extremely potent cytotoxic activity with IC50 values of 10(-12) M-10(-9) M on HeLa S3 cell. Three different producing strains isolated from soils were taxonomically assigned as Streptomyces. Duocarmycin A was unstable in culture broth, so improved culture conditions were designed to produce a high titer of duocarmycins B1, B2, C1 and C2 which are halogenated seco-compounds of duocarmycin A. Duocarmycin SA, one of the most potent cytotoxic agents yet discovered, was shown to be more stable in culture media than duocarmycin A, despite the structural similarity on their spirocyclopropylhexadienone moiety. In contrast to the duocarmycin A fermentation, no halogenated seco-compounds of duocarmycin SA were detected in culture broth supplemented with Br- or Cl-. All duocarmycins could be produced using one producing strain with improved media and culture conditions.
在我们寻找新型抗肿瘤抗生素的过程中发现了六种双炔霉素，它们对HeLa S3细胞表现出极强的细胞毒性活性，IC50值为10(-12)M - 10(-9)M。从土壤中分离出的三种不同产生菌在分类学上被归为链霉菌属。双炔霉素A在培养液中不稳定，因此设计了改进的培养条件以高产率生产双炔霉素B1、B2、C1和C2，它们是双炔霉素A的卤代开环化合物。双炔霉素SA是迄今发现的最有效的细胞毒性剂之一，尽管其螺环丙基己二烯酮部分结构相似，但在培养基中比双炔霉素A更稳定。与双炔霉素A发酵不同，在添加Br-或Cl-的培养液中未检测到双炔霉素SA的卤代开环化合物。使用一种产生菌并改进培养基和培养条件就能生产所有的双炔霉素。
