Piperazimycins:: Cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces
Piperazimycins:: Cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces
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DOI：
10.1021/jo061064g
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发表时间：
2007-01-19
影响因子：
3.6
通讯作者：
Fenical, William
中科院分区：
文献类型：
--
作者：
Miller, Eric D.;Kauffman, Christopher A.;Fenical, William
三种有效的癌细胞毒素，哌嗪霉素A-C（1-3），已经从链霉菌的发酵液中分离出来，从关岛附近的海洋沉积物中培育而成。这些环状hexadepsipeptides的结构通过光谱，化学和晶体学方法的组合进行分配。哌嗪霉素由稀有氨基酸组成，包括羟基乙酸、α-甲基丝氨酸、γ-羟基哌嗪酸和γ-氯哌嗪酸。发现新的氨基酸残基2-氨基-8-甲基-4，6-壬二烯酸和2-氨基-8-甲基-4，6-癸二烯酸分别为哌嗪霉素A和C的组分。当在国家癌症研究所的60种癌细胞系小组中筛选时，哌嗪霉素A对多种肿瘤细胞系表现出有效的体外细胞毒性，平均GI（50）为100 nM。
[graphics]Three potent cancer cell cytotoxins, piperazimycins A-C (1-3), have been isolated from the fermentation broth of a Streptomyces sp., cultivated from marine sediments near the island of Guam. The structures of these cyclic hexadepsipeptides were assigned by a combination of spectral, chemical, and crystallographic methods. The piperazimycins are composed of rare amino acids, including hydroxyacetic acid, alpha-methylserine, gamma-hydroxypiperazic acid, and gamma-chloropiperazic acid. The novel amino acid residues 2-amino-8-methyl-4,6-nonadienoic acid and 2-amino-8-methyl-4,6-decadienoic acid were found as components of piperazimycins A and C, respectively. When screened in the National Cancer Institute's 60 cancer cell line panel, piperazimycin A exhibited potent in vitro cytotoxicity toward multiple tumor cell lines with a mean GI(50) of 100 nM.