Plakortides, novel cyclic peroxides from the sponge Plakortis halichondrioides: activators of cardiac SR-CA(2+)-pumping ATPase.
As part of a search for novel activators of Ca2+ pumping activity of cardiac SR- (sarcoplasmic reticulum), the EtOAc extract of the Jamaican sponge Plakortis halichondrioides was shown to be active. Bioassay-guided fractionation of the extract followed by preparative TLC and HPLC yielded several known and novel compounds. Three of the novel cyclic peroxides, plakortides F, G, and H (3, 4, and 5) are the subject of this report. Their structures including relative stereochemistry were established by interpretation of spectral data. Micromolar concentrations of plakortides F-H (3-5) were found to significantly enhance Ca2+ uptake by SR.
Patil
A D
AD
Department of Biomolecular Discovery, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. Inet: Ashok_D_Patil@sbphrd.com
Freyer
A J
AJ
Carte
B
B
Johnson
R K
RK
Lahouratate
P
P
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004146:Dioxanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009206:Myocardium / Q000201:enzymology*; D011161:Porifera / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D004146:Dioxanes; C102699:plakortide F; C102700:plakortide G; C102701:plakortide H; D000252:Calcium-Transporting ATPases