Cylindrocyclophanes with Proteasome Inhibitory Activity from the Cyanobacterium Nostoc sp.
Cylindrocyclophanes with Proteasome Inhibitory Activity from the Cyanobacterium Nostoc sp.
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DOI：
10.1021/np100352e
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发表时间：
2010-09-01
影响因子：
5.1
通讯作者：
Orjala, Jimmy
中科院分区：
文献类型：
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作者：
Chlipala, George E.;Sturdy, Megan;Orjala, Jimmy
从芝加哥市的一个公园道路上收集的材料提供了一种Nostoc物种（UIC 10022A）的分离。该菌株提取物对肿瘤细胞HT29、MCF7、NCI-H460、SF268具有明显的抑制作用和抗增殖活性。标准化的重复实验方案允许从不到100毫克的有机提取物中快速鉴定3个已知的（11-13）和9个新的（1-9）氯化圆柱环番。LC-UV-MS数据指导从较大的提取物中放大分离1-9和11-13。此外，培养基的KBr富集提供了溴化圆柱环烷的分离（10）。对1 ~ 5、9、10 ~ 13的生物学评价揭示了其对20S蛋白酶体的大范围活性，初步确定了柱环磷酰胺药效团的结构与活性关系。
Material collected from a parkway in the city of Chicago afforded the isolation of a Nostoc species (UIC 10022A). The extract of this strain displayed significant inhibition of the 20S proteasome as well as antiproliferative activity against HT29, MCF7, NCI-H460, and SF268 cancer cell lines. A standardized dereplication protocol allowed for the rapid identification of three known (11-13) and nine new (1-9) chlorinated cylindrocyclophanes from less than 100 mg of organic extract. Scale-up isolation of 1-9 and 11-13 from a larger extract was guided by LC-UV-MS data. In addition, KBr enrichment of the culture media afforded the isolation of a brominated cylindrocyclophane (10). Biological evaluation of 1-5, 9, and 10-13 revealed a large range of activity against the 20S proteasome and allowed the determination of preliminary structure activity relationships of the cylindrocyclophane pharmacophore.