Plakortides, Novel Cyclic Peroxides from the Sponge Plakortis halichondrioides: Activators of Cardiac SR-CA²⁺-Pumping ATPase

Abstract

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.

New cytotoxic cyclic peroxide acids from Plakortis sp. marine sponge

“…They include plakinic acids the strongly antifungal peroxyketals named peroxyplakoric acids and the recently reported activators of cardiac SR-Ca 2+ ATPase plakortones A-D. In addition, 6-10 an unusual furano α, β–unsaturated ester ( 6,7 ) has also been described. 4,11,12 …”

Peroxy natural products

“…44 An Okinawan specimen of the same species provided two futher cytotoxic endoperoxides, haterumadioxins A and B 87 and 88 with moderate cytotoxicity. 45 Plakortide F, originally isolated from P. Halichondrioides, 46 …”

The Marine Sponge-Derived Polyketide Endoperoxide Plakortide F Acid Mediates Its Antifungal Activity by Interfering with Calcium Homeostasis

“…For example, the compound plakorin, isolated from an unidentified species of Plakortis collected in Okinawa, Japan, was shown to activate a SERCA transporter in rabbit skeletal muscle (27). Similarly, in a screening for SERCA activators, four different metabolites (3-epiplakortin and plakortides F, G, and H) isolated from the Jamaican sponge Plakortis halichondrioides were found to stimulate cardiac Ca 2ϩ uptake in sarcoplasmic reticulum vesicles from canine ventricle tissue (29). While these results are intriguing, it remains to be determined whether the activation of sarcoplasmic reticulum Ca 2ϩ ATPase reflects the primary mechanism of action of marine cyclic peroxides.…”