Cylindrocyclophanes with Proteasome Inhibitory Activity from the Cyanobacterium Nostoc sp.

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• 作者：George E. Chlipala ; Megan Sturdy ; Aleksej Krunic ; Daniel D. Lantvit ; Qi Shen ; Kyle Porter ; Steven M. Swanson ; Jimmy Orjala
• 刊名：Journal of Natural Products
• 出版年：2010
• 出版时间：September 24, 2010
• 年：2010
• 卷：73
• 期：9
• 页码：1529-1537
• 全文大小：262K
• 年卷期：v.73,no.9(September 24, 2010)
• ISSN：1520-6025

文摘

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.