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Cylindrocyclophanes with Proteasome Inhibitory Activity from the Cyanobacterium Nostoc sp.

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journal contribution
posted on 24.09.2010, 00:00 by George E. Chlipala, Megan Sturdy, Aleksej Krunic, Daniel D. Lantvit, Qi Shen, Kyle Porter, Steven M. Swanson, Jimmy Orjala
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 (1113) and nine new (19) chlorinated cylindrocyclophanes from less than 100 mg of organic extract. Scale-up isolation of 19 and 1113 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 15, 9, and 1013 revealed a large range of activity against the 20S proteasome and allowed the determination of preliminary structure−activity relationships of the cylindrocyclophane pharmacophore.