title: Cylindrocyclophanes with proteasome inhibitory activity from the Cyanobacterium Nostoc sp.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Chlipala
authors.forename: Megan
authors.initials: M
authors.lastname: Sturdy
authors.forename: Aleksej
authors.initials: A
authors.lastname: Krunic
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Kyle
authors.initials: K
authors.lastname: Porter
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: Jimmy
authors.initials: J
authors.lastname: Orjala
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002641:Chicago; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D046937:Nostoc / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011084:Polycyclic Aromatic Hydrocarbons; D061988:Proteasome Inhibitors; C434087:cylindrocyclophane A
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