Carteriosulfonic acids A-C, GSK-3beta inhibitors from a Carteriospongia sp.
Modulators of Wnt signaling have therapeutic potential in a number of human diseases. A fractionated library from marine invertebrates was screened in a luciferase assay designed to identify modulators of Wnt signaling. A fraction from a Carteriospongia sp. sponge activated Wnt signaling and was subsequently shown to inhibit GSK-3beta, which inhibits Wnt signaling through phosphorylation of beta-catenin. Three novel natural products, carteriosulfonic acids A (1), B (2), and C (3), were identified as active constituents. The carteriosulfonic acids contain unprecedented 4,6,7,9-tetrahydroxylated decanoic acid subunits. Their structures were elucidated through analysis of NMR data and a detailed analysis of pseudo MS(3) spectra.
McCulloch
Malcolm W B
MW
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Bugni
Tim S
TS
Concepcion
Gisela P
GP
Coombs
Gary S
GS
Harper
Mary Kay
MK
Kaur
Simran
S
Mangalindan
Gina C
GC
Mutizwa
Misha M
MM
Veltri
Charles A
CA
Virshup
David M
DM
Ireland
Chris M
CM
D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009792:Oceans and Seas; D011161:Porifera / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051153:Wnt Proteins / Q000187:drug effects / Q000378:metabolism*
D013451:Sulfonic Acids; D051153:Wnt Proteins; C544283:carteriosulfonic acid A; C544284:carteriosulfonic acid B; C544285:carteriosulfonic acid C; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3