The chemistry, mechanism of action and biological properties of CC-1065, a potent antitumor antibiotic.
The chemistry, mechanism of action and biological properties of CC-1065, a potent antitumor antibiotic.
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DOI：
10.7164/antibiotics.39.319
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发表时间：
1986-03
期刊：
影响因子：
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通讯作者：
VINCENT L. Reynolds;J. Mcgovren;LAURENCE H. Hurley
中科院分区：
文献类型：
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作者：
VINCENT L. Reynolds;J. Mcgovren;LAURENCE H. Hurley
CC-1065的结构（图1）通过X射线晶体学测定5，6）。在分离用于X射线衍射数据收集的CC-1065的合适晶型之前，将CC-1065与异氰酸乙酯在吡啶中反应获得的化学降解产物（1）结晶，并通过X射线晶体学确定其结构。一种密切相关的化合物PDE I（2）以前曾从发酵液中分离出来，但在200 mg/kg剂量下对小鼠无毒。这与CC-1065形成鲜明对比，CC-1065在0.1 mg/kg的剂量下是有毒的。5）最近，CC-1065的碱性和酸性水解产物已被纯化和表征。CC-1065（NSC-298223）是由Streptomyces zelensis NRRL 11，183产生的极其有效的抗肿瘤抗生素。Upjohn公司的研究人员通过筛选土壤培养物中对培养物中的L1210细胞具有细胞毒性活性和对小鼠P388白血病具有体内活性的药物，分离出了产生这种抗生素的微生物1 ~3）。CC 1065的生产、其体外生物活性、微生物测定和分类学已被描述1），并且最近改进的用于生产和分离该化合物的方法也被描述3）。CC-1065也被苏联科学家从链霉菌中分离出来。S. zelensis仅产生非常少量的CC-1065（约6 - 9 mg/L）3），并且参与分离和处理这种有效抗肿瘤剂的实验室工作人员需要采取预防措施。
The structure of CC-1065 (Fig. 1) was determined by X-ray crystallography5,6). Prior to isolation of a suitable crystalline form of CC-1065 for X-ray diffraction data collection, a chemical degradation product (1) obtained by reaction of CC-1065 with ethyl isocyanate in pyridine was crystallized and its structure determined by X-ray crystallography". A closely related compound, PDE I (2), was previously isolated from a fermentation broth8), but is nontoxic in mice at 200 mg/kg. This is in sharp contrast to CC-1065, which is toxic at a dose of 0.1 mg/kg5) Recently the products of alkaline and acidic hydrolysis of CC-1065 have been purified and characterized'). CC-1065 (NSC-298223) is an extremely potent antitumor antibiotic produced by Streptomyces zelensis NRRL 11,183. The microorganism producing this antibiotic was isolated by investigators at The Upjohn Company by screening soil cultures for agents displaying both cytotoxic activity against L1210 cells in culture and in vivo activity against P388 leukemia in mice1~3). The production of CC1065, its in vitro biological activity, microbiological assays and taxonomy have been described1), and more recently improved methods for production and isolation of this compound have also been published3). CC-1065 has also been isolated by scientists in the USSR from Streptomyces canulus4). Fermentation broths of S. zelensis produce only very modest amounts of CC-1065 (approximately 6 9 mg/liter)3) and precautions need to be taken by laboratory workers involved in the isolation and handling of this potent antitumor agent.