Protein phosphatase inhibitors isolated from Spongia irregularis collected in Papua New Guinea.
Irregularasulfate (1), a new nitrogen-containing sesterterpenoid, and the known sesterterpenoids hipposulfate C (2), halisulfate-7 (3), and igernellin (4), have been isolated from the marine sponge Spongia irregularis collected in Papua New Guinea. The structure of 1 was elucidated via analysis of its spectroscopic data. Sesterterpenoids 1, 2, and 3 are moderate inhibitors of the catalytic subunits of the mammalian Ser/Thr protein phosphatases calcineurin, PP-1, and PP-2A. The phosphate analogue of 3 and the thiophosphate analogue of 2 have been prepared from the corresponding natural products and evaluated for their ability to inhibit the phosphatase activity of calcineurin.
Carr
Gavin
G
Departments of Chemistry and Earth & Ocean Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
Raszek
Mikolaj
M
Van Soest
Rob
R
Matainaho
Teatulohi
T
Shopik
Micheal
M
Holmes
Charles F B
CF
Andersen
Raymond J
RJ
D000818:Animals; D065095:Calcineurin Inhibitors; D008386:Marine Biology; D015394:Molecular Structure; D010219:Papua New Guinea; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011161:Porifera / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D054830:Sesterterpenes; D013729:Terpenes; C400351:halisulfate 7; C525477:hipposulfate C; C525478:igernellin; C525476:irregularasulfate; D010749:Phosphoprotein Phosphatases