Cylindrocyclophanes with proteasome inhibitory activity from the Cyanobacterium Nostoc sp.
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.
Chlipala
George E
GE
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Sturdy
Megan
M
Krunic
Aleksej
A
Lantvit
Daniel D
DD
Shen
Qi
Q
Porter
Kyle
K
Swanson
Steven M
SM
Orjala
Jimmy
J
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
D000970:Antineoplastic Agents; D011084:Polycyclic Aromatic Hydrocarbons; D061988:Proteasome Inhibitors; C434087:cylindrocyclophane A
Int J Gynecol Cancer. 2006 Jan-Feb;16(1):71-6
16445613
J Nat Prod. 1996 Apr;59(4):427-30
8699186
J Nat Prod. 2001 Jan;64(1):54-9
11170666
J Nat Prod. 2007 Apr;70(4):499-503
17311455
J Nat Prod. 2002 Jun;65(6):866-71
12088429
Cancer Cell. 2004 May;5(5):417-21
15144949
Eur J Cancer. 2004 Oct;40(15):2217-29
15454246
Nat Chem Biol. 2008 Jan;4(1):69-74
18059261
Pharm Biol. 2009 Jan;47(1):53-60
21430788
Cancer Chemother Pharmacol. 1999;43(2):115-25
9923816
Phytochemistry. 2007 Apr;68(7):954-79
17336349
Chembiochem. 2006 Feb;7(2):229-38
16247831
J Nat Prod. 2009 Mar 27;72(3):540-53
19245259
Int J Syst Evol Microbiol. 2005 Jan;55(Pt 1):11-26
15653847
Chembiochem. 2008 Nov 3;9(16):2692-703
18924217
Cell. 1994 Oct 7;79(1):13-21
7923371
Appl Environ Microbiol. 1997 Aug;63(8):3327-32
9251225
J Nat Prod. 2001 Nov;64(11):1483-5
11720542
J Immunol. 2006 May 15;176(10):6302-12
16670342
Planta Med. 1995 Aug;61(4):321-8
7480178
J Nat Prod. 2001 May;64(5):572-7
11374946
J Nat Prod. 1997 Jul;60(7):724-6
9249979
Lung Cancer. 2003 Feb;39(2):197-9
12581573
Mol Biol Evol. 2007 Aug;24(8):1596-9
17488738
J Nat Prod. 2000 Nov;63(11):1524-6
11087597