Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp.
Three new sterol sulfates, spheciosterol sulfates A-C (1-3), and the known sterol sulfate topsentiasterol sulfate E (4) have been isolated from the sponge Spheciospongia sp., collected in the Philippines. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-4 inhibited PKCzeta with IC50 values of 1.59, 0.53, 0.11, and 1.21 microM, respectively. In a cell-based assay, 1-4 also inhibited NF-kappaB activation with EC50 values of 12-64 microM.
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Emily L
EL
Whitson
Tim S
TS
Bugni
Priya S
PS
Chockalingam
Gisela P
GP
Concepcion
Mary Kay
MK
Harper
Min
M
He
John N A
JN
Hooper
Gina C
GC
Mangalindan
Frank
F
Ritacco
Chris M
CM
Ireland
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes; D016328:NF-kappa B / Q000187:drug effects*; D010679:Philippines; D011161:Porifera / Q000737:chemistry*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013261:Sterols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D007527:Isoenzymes; D016328:NF-kappa B; D013261:Sterols; D013463:Sulfuric Acid Esters; C531484:spheciosterol sulfate A; C531485:spheciosterol sulfate B; C531486:spheciosterol sulfate C; D011493:Protein Kinase C