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Five novel biscembranoids, ximaolides H–L (1–5), were isolated from the Hainan soft coral Sarcophyton tortuosum. Compounds 1and 2are the first examples of biscembranoids bearing a 135-bridged lactone moiety, 4is the first biscembranoid comprising an uncommon oxetane ring, and 5represents the first 36-peroxyl biscembranoid.

Eight polycyclic furanobutenolide-containing norcembrane diterpenoids featuring C19 frameworks (1–8) were rapidly recognized and isolated from the Hainan soft coral Sinulariasp. by the HSQC-based small molecule accurate recognition technology. Yonarolide A (1a), featuring an unprecedented 5/6/4/4/7 pentacyclic ring skeleton, was surprisingly obtained as a transformed product by leaving compound 1under indoor natural light, and was further proved to be a [2 + 2] cycloaddition product of 1by photochemical reaction. The absolute stereochemistry of 1aand the three known norcembrane diterpenoids 1, 4, and 7were determined by using X-ray diffraction (XRD) analyses. Further, with the aid of XRD analysis, the structure of scabrolide B (2), which was previously reported of possessing 5/6/7 tricyclic skeleton, was firmly revised as 2awith the rare inelegane skeleton featured by the highly oxygenated 5/7/6 tricyclic carbocycle.

The marine natural product scalaradial (SLD) is a potent inhibitor of secretory phospholipase A2 (sPLA2). Our previous work has demonstrated that SLD inhibits epidermal growth factor receptor-mediated Akt phosphorylation, and this effect is independent of sPLA2. Here we report the role of SLD in extracellular signal-regulated kinase (ERK)1/2 activation. SLD inhibited ERK1/2 phosphorylation within the first 15 min (early inhibition), then stimulated ERK1/2 phosphorylation after 15 min of SLD treatment (late stimulation) in BEL-7402 cells, displaying biphasic regulatory features. Other PLA2 inhibitors such as the cytosolic and Ca2+-independent PLA2 inhibitor methyl arachidonyl fluorophosphonate, and another sPLA2 inhibitor, thioetheramide-phosphatidylcholine, only transiently inhibited ERK1/2 phosphorylation and did not display the stimulatory effect. The early inhibition of ERK1/2 phosphorylation by SLD was reversed by the PLA2 metabolite arachidonic acid, while the late stimulation was abrogated by constitutively active myristolated-Akt. Furthermore, SLD dose- and time-dependently inhibited the phosphorylation of Raf-1 on Ser 259, which is an established event by which Akt inhibits ERK 1/2 activation. Taken together, these data demonstrate a biphasic regulation of ERK1/2 phosphorylation by SLD in a time-dependent manner, i.e., early inhibition and late stimulation. The early inhibition of ERK1/2 phosphorylation is mediated by sPLA2, at least in part, and the late stimulation is effected through SLD inhibition of Akt. These findings provide further insight into the mechanisms underlying the pharmacological effect of SLD.

The marine natural product 12-epi-scalaradial (SLD) is a specific secretory phospholipase A2(sPLA2) inhibitor. However, little is known about whether this compound has other pharmacological effects. Here, we revealed a novel effect of SLD on epidermal growth factor receptor (EGFR)-mediated Akt phosphorylation. SLD dose- and time-dependently inhibited epidermal growth factor (EGF)-stimulated Akt phosphorylation, which is required for Akt activation. SLD also blocked the EGF-stimulated membrane translocation of 3-phosphoinositide-dependent protein kinase 1 and inhibited phosphatidylinositol 3-kinase activity. This inhibition is specific for SLD because other phospholipase inhibitors, including sPLA2inhibitor thioetheramide-phosphatidylcholine, cytosolic PLA2inhibitor arachidonyl trifluoromethyl ketone, cytosolic PLA2and Ca2+-independent PLA2inhibitor methyl arachidonyl fluorophosphonate, phospholipase C inhibitor U73122, and cyclooxygenases inhibitor indomethacin, failed to inhibit EGF-stimulated Akt phosphorylation. Furthermore, arachidonic acid, the main sPLA2-catalyzed metabolite, was not able to rescue SLD inhibition of EGF-stimulated Akt phosphorylation. Overexpression of group IIA or group X sPLA2did not reverse the inhibitory effect of SLD on Akt phosphorylation, either. Our results demonstrate that SLD inhibits EGFR-mediated Akt phosphorylation, and this novel effect of SLD is independent of sPLA2.

The marine natural product 12-epi-scalaradial (SLD) is a specific secretory phospholipase A(2) (sPLA(2)) inhibitor. However, little is known about whether this compound has other pharmacological effects. Here, we revealed a novel effect of SLD on epidermal growth factor receptor (EGFR)-mediated Akt phosphorylation. SLD dose- and time-dependently inhibited epidermal growth factor (EGF)-stimulated Akt phosphorylation, which is required for Akt activation. SLD also blocked the EGF-stimulated membrane translocation of 3-phosphoinositide-dependent protein kinase 1 and inhibited phosphatidylinositol 3-kinase activity. This inhibition is specific for SLD because other phospholipase inhibitors, including sPLA(2) inhibitor thioetheramide-phosphatidylcholine, cytosolic PLA(2) inhibitor arachidonyl trifluoromethyl ketone, cytosolic PLA(2) and Ca(2+)-independent PLA(2) inhibitor methyl arachidonyl fluorophosphonate, phospholipase C inhibitor U73122, and cyclooxygenases inhibitor indomethacin, failed to inhibit EGF-stimulated Akt phosphorylation. Furthermore, arachidonic acid, the main sPLA(2)-catalyzed metabolite, was not able to rescue SLD inhibition of EGF-stimulated Akt phosphorylation. Overexpression of group IIA or group X sPLA(2) did not reverse the inhibitory effect of SLD on Akt phosphorylation, either. Our results demonstrate that SLD inhibits EGFR-mediated Akt phosphorylation, and this novel effect of SLD is independent of sPLA(2).

The structure of hurghadin ( 1), a pigment from the Red Sea nudibranch Hexabranchus sanguineus, was elucidated by interpretation of spectral data and by chemical method.

AbstractFour new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6–9), together with two known analogues 2aand 2b, were isolated from a Red Sea sponge Hippospongiasp. Their structures were elucidated by extensive spectroscopic studies.

AbstractFour new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6–9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongiasp. Their structures were elucidated by extensive spectroscopic studies.

The absolute stereochemistry of the quinolizidone systems present in the marine macrocyclic alkaloids isosaraine-1 ( 3) and isosaraine-2 ( 4), minor metabolites of the Mediterranean sponge Reniera sarai, has been established by applying advanced Mosher's method to the alcohol derivatives ( 5and 6).

A new norsesterterpene cyclic peroxide, named hurghaperoxide (1), has been isolated from an undescribed Red Sea sponge. The structure of this novel molecule was determined mainly by detailed spectroscopic analysis.

Four new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6-9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.

Four new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6-9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.