Identification of a marine-derived sesquiterpenoid, Compound-8, that inhibits tumour necrosis factor-induced cell death by blocking complex II assembly.

BACKGROUND AND PURPOSE: Tumour necrosis factor (TNF) is a pleiotropic inflammatory cytokine that not only directly induces inflammatory gene expression but also triggers apoptotic and necroptotic cell death, which leads to tissue damage and indirectly exacerbates inflammation. Thus, identification of inhibitors for TNF-induced cell death has broad therapeutic relevance for TNF-related inflammatory diseases. In the present study, we isolated and identified a marine fungus-derived sesquiterpenoid, 9α,14-dihydroxy-6ß-p-nitrobenzoylcinnamolide (named as Cpd-8), that inhibits TNF receptor superfamily-induced cell death by preventing the formation of cytosolic death complex II. EXPERIMENTAL APPROACH: Marine sponge-associated fungi were cultured and the secondary metabolites were extracted to yield pure compounds. Cell viability was measured by ATP-Glo cell viability assay. The effects of Cpd-8 on TNF signalling pathway were investigated by western blotting, immunoprecipitation, and immunofluorescence assays. A mouse model of acute liver injury (ALI) was employed to explore the protection effect of Cpd-8, in vivo. KEY RESULTS: Cpd-8 selectively inhibits TNF receptor superfamily-induced apoptosis and necroptosis. Cpd-8 prevents the formation of cytosolic death complex II and subsequent RIPK1-RIPK3 necrosome, while it has no effect on TNF receptor I (TNFR1) internalization and the formation of complex I in TNF signalling pathway. In vivo, Cpd-8 protects mice against TNF-α/D-GalN-induced ALI. CONCLUSION AND IMPLICATIONS: A marine fungus-derived sesquiterpenoid, Cpd-8, inhibits TNF receptor superfamily-induced cell death, both in vitro and in vivo. This study not only provides a useful research tool to investigate the regulatory mechanisms of TNF-induced cell death but also identifies a promising lead compound for future drug development.

Coriaceumins A-D, the First Nitrogen-Containing Crenulide Diterpenoids from the Brown Alga Dictyota coriacea Collected in the East China Sea.

A phytochemical investigation of an East China Sea collection of the brown alga Dictyota coriacea has led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A-D (1-4), two rare nitrogenous xenicane diterpenoids, dictyolactams C (5) and D (6), and one known crenulide diterpenoid, hydroxycrenulide (7). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations. Coriaceumins A-D (1-4) represent the first examples of nitrogen-containing crenulide diterpenoids. In a bioassay, compounds 2, 3, 5, and 7 were found to exhibit different levels of inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) with IC50 values ranging from 7.3 to 19 µM. In addition, the primary structure-activity relationships of all the isolates were summarized.

Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

Coumaronochromones, flavanones, and isoflavones from the twigs and leaves of Erythrina subumbrans inhibit PTP1B and nitric oxide production.

A chemical investigation of the twigs and leaves of Erythrina subumbrans led to the isolation and structural elucidation of three coumaronochromones, erythrinasubumbrin A and (±)-erythrinasubumbrin B, five prenylated flavanones, (±)-erythrinasubumbrin C and erythrinasubumbrins D-F, and two prenylated isoflavones, (±)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, in addition to 18 known analogues. Two extra cinnamylphenols previously only known as commercial synthetic products were also isolated and elucidated from a natural source for the first time, and assigned the trivial names erythrinasubumbrins G and H. Their structures were characterized by detailed analysis of spectroscopic data, including HRESIMS and 2D NMR. The absolute configurations of the previously undescribed isolates and the known coumaronochromone lupinol C were determined by specific rotation and electronic circular dichroism (ECD) data. All the isolates were evaluated for their inhibitory activities on protein tyrosine phosphatase 1 B (PTP1B) and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells as well as their cytotoxicity against the HCT116 cell line. The pair of enantiomers, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone and (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 4'-O-methyl-8-prenylnaringenin, glepidotin B, shuterin, parvisoflavones A, luteone, lupiwighteone, 2,3-dehydrokievitone, 6,8-diprenylgenistein, angustone A, and 2'-O-demethylbidwillol B exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.21 to 19.17 µM, while erythrinasubumbrin A, (-)-erythrinasubumbrin B, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 8-prenylnaringenin, macatrichocarpin A, alpinumisoflavone, and 2'-O-demethylbidwillol B substantially inhibited NO production in BV-2 microglial cells. In addition, 8-prenylnaringenin showed weak cytotoxicity with an IC50 value of 9.13 µM. This is the first report of PTP1B inhibitory activity for a coumaronochromone.

Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii.

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ± 1.09 µM.

Rearranged Diels-Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra.

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).

Neuronal Modulators from the Coral-Associated Fungi Aspergillus candidus.

Three new p-terphenyl derivatives, named 4″-O-methyl-prenylterphenyllin B (1) and phenylcandilide A and B (17 and 18), and three new indole-diterpene alkaloids, asperindoles E-G (22-24), were isolated together with eighteen known analogues from the fungi Aspergillus candidus associated with the South China Sea gorgonian Junceela fragillis. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic analysis, and DFT/NMR and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, the compounds 6, 9, 14, 17, 18 and 24 modulated spontaneous Ca2+ oscillations and 4-aminopyridine hyperexcited neuronal activity. A preliminary structure-activity relationship was discussed.

Structurally diverse halosesquiterpenoids from the red alga Laurencia composita Yamada.

A phytochemical investigation on the MeOH extract of the red alga Laurencia composita Yamada led to the discovery of six new highly halogenated sesquiterpenoids, including two bisabolane-type sesquiterpenoids (1 and 2), one nerolidol derivative (7), and three chamigrane-type sesquiterpenoids (9, 10, and 18), together with 13 known sesquiterpenoids. Their structures, including relative configuration, were elucidated by extensive spectroscopic analysis, and by comparison with data for related known compounds. The absolute configuration at C-10 of laurecomposin A (1) was determined by the modified Mosher's method. Halonerolidol (7) is the first naturally occurring halogenated nerolidol derivative, while compositacin L (9) represents the third example of chamigranes having a C-10 carbonyl group. Antifungal, antibacterial, and receptor tyrosine kinase inhibitory activities of these isolates were evaluated. The results showed that compounds 1-3 and 5 exhibited significant antifungal activity against Microsporum gypseum (Cmccfmza) with MIC values of 4, 8, 8, and 4 µg/mL, respectively. Additionally, compounds 1-3 and 5 also displayed promising antibacterial activity against Gram-positive bacteria Staphylococcus aureus Newman strain with MIC values ranging from 10.9 to 26.8 µg/mL.

Cembrane-type diterpenoids from the South China Sea soft coral Sarcophyton mililatensis.

Eight cembrane-type diterpenoids, namely, (+)-(6R)-6-hydroxyisosarcophytoxide (1), (+)-(6R)-6-acetoxyisosarcophytoxide (2), (+)-17-hydroxyisosarcophytoxide (3), sarcomililatins A-D (4-7), and sarcomililatol (8), were isolated from the soft coral Sarcophyton mililatensis collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide (9) and (+)-isosarcophine (10). The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound 1 was established by the modified Mosher׳s method, while the absolute configurations of compounds 4 and 5 were assigned by electronic circular dichroism (ECD) spectroscopy and that of compound 8 was established by time-dependent density functional theory electronic circular dichroism (TD-DFT ECD) calculation. In in vitro bioassays, compound 9 displayed significant cytotoxicity against the human cancer cell lines human promyelocytic leukemia cells (HL-60) and human lung adenocarcinoma cells (A-549) with IC50 values of 0.78±0.21 and 1.26±0.80 µmol/L, respectively. Compounds 4 and 9 also showed moderate inhibitory effects on the TNFα-induced Nuclear factor kappa B (NF-κB, a therapeutical target in cancer) activation, showing IC50 values of 35.23±12.42 and 22.52±4.44 µmol/L, respectively.

Dictyoptesterols A-C, ∆22-24-oxo cholestane-type sterols with potent PTP1B inhibitory activity from the brown alga Dictyopteris undulata Holmes.

Three new cholestane-type sterols bearing an unusual ∆22-24-oxo side chain, namely, dictyoptesterols A-C (1-3), were isolated from the brown alga Dictyopteris undulata Holmes, together with five known strutural analogues (4-8). Their structures were elucidated on the basis of by extensive spectroscopic analysis. The absolute configurations of the steroidal nuclei of the new compounds were proposed by a comparison of NMR data with those of related known compounds as well as biogenetic considerations. All of the isolates were evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B (PTP1B) activity. The results showed that compounds 1-5 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.03 ±â€¯0.76 to 15.01 ±â€¯2.88 µM. In particular, compounds 3 and 4 showed promising inhibitory effects towards PTP1B with IC50 values of 3.03 ±â€¯0.76 and 3.72 ±â€¯0.40 µM, respectively, when compared to the positive control oleanolic acid (IC50, 2.83 ±â€¯0.39 µM). The chemotaxonomic significance of these isolated ∆22-24-oxo cholestanes has also been discussed.

PTP1B inhibitory and cytotoxic C-24 epimers of Δ28-24-hydroxy stigmastane-type steroids from the brown alga Dictyopteris undulata Holmes.

Ten stigmastane-type steroids bearing unusual Δ28-24-hydroxy side chains, dictyopterisins A-J, including three pairs of C-24 epimers, dictyopterisins B/C, F/G, and I/J, were isolated from the brown alga Dictyopteris undulata Holmes, together with two previously reported analogues, (24S)- and (24R)-saringosterol. Their structures were elucidated on the basis of extensive spectroscopic analysis, with their absolute configurations at the stereogenic center C-24 of the side chain being assigned by a direct comparison of 1H NMR data with those of related known compounds. The absolute configurations of the steroidal nuclei of dictyopterisins A, B, and H were determined using the modified Mosher's method. The mixture of dictyopterisins D and E and dictyopterisin I exhibited promising PTP1B inhibitory activities with IC50 values of 1.88 and 3.47 µM, respectively, comparable to the positive control oleanolic acid (IC50, 2.78 µM). In addition, the mixture of dictyopterisins D and E and dictyopterisins F-J displayed significant cytotoxicities against the human cancer cell lines HL-60 (IC50 from 1.02 to 2.70 µM) and A-549 (IC50 from 1.35 to 2.85 µM).

Two pairs of rare naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives from the red alga Chondria crassicaulis.

Two pairs of rare naturally occurring racemic lipids, (±)-4,7-dihydroxy-4-methyl-2,5-heptanedione (1), and (±)-7-butoxy-4-hydroxy-4-methyl-2,5-heptanedione (2) were isolated from the red alga Chondria crassicaulis Harv. The structures of the racemic mixtures of 1 and 2 were elucidated by detailed spectroscopic techniques, including 1D and 2D NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments, and by comparison with data for related known analogs. This is the first report of naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives. Antifungal, PTP1B inhibitory, and receptor tyrosine kinase inhibitory activities of these two compounds were investigated. The results showed that compounds 1 and 2 exhibited good selective inhibition against RET tyrosine kinase activity with IC50 values of 9.56 and 8.93 µM, respectively. Compound 1 also displayed moderate antifungal activity against Cryptococcus neoformans (32609), showing a MIC80 value of 32 µg/ml.

Aglaiabbrevins A-D, New Prenylated Bibenzyls from the Leaves of Aglaia abbreviata with Potent PTP1B Inhibitory Activity.

Four new prenylated bibenzyls, named aglaiabbrevins A-D (2, 4-6), were isolated from the leaves of Aglaia abbreviata, along with two known related analogues, 3,5-dihydroxy-2-[3,7-dimethyl-2(E),6-octadienyl]bibenzyl (7) and 3,5-dihydroxy-2-(3-methyl-2-butenyl)bibenzyl (8). The structures of the new compounds were elucidated on the basis of extensive spectroscopic experiments, mainly one and two dimensional (1D- and 2D)-NMR, and the absolute configuration of 5 was determined by the measurement of specific rotation. The isolated compounds were evaluated for their protein tyrosine phosphatase-1B (PTP1B) inhibitory activity. The results showed that compounds 5-7 exhibited more potent PTP1B inhibitory effects with IC50 values of 2.58±0.52, 2.44±0.35, and 2.23±0.14 µM, respectively, than the positive control oleanolic acid (IC50=2.74±0.20 µM). On the basis of the data obtained, these bibenzyls with the longer C-2 prenyl groups may be considered as potential lead compounds for the development of new anti-obesity and anti-diabetic agents. Also, the PTP1B inhibitory effects for prenylated bibenzyls are being reported for the first time.

Compositacins A-K: Bioactive chamigrane-type halosesquiterpenoids from the red alga Laurencia composita Yamada.

Eleven highly halogenated chamigrane sesquiterpenoids, compositacins A-K, including one unusual rearranged chamigrane sesquiterpenoid, compositacin A, were isolated from the red alga Laurencia composita Yamada, along with seven known structural analogues. Compositacins B and D are the first examples of chamigranes bearing an ether bridge involving C-5/C-9 and C-3/C-5, respectively, while compositacins B and C represent the first chamigranes with a C-10 carbonyl group. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compositacin B was determined by ECD calculation, whereas the absolute configurations of compositacins A and C-L were proposed on biosynthetic grounds by comparison to compositacin B and the related known sesquiterpenoids johnstonol and yicterpene A. We also suggest that the structure of the previously reported sesquiterpenoid laurokamin A should be revised. Cytotoxicity and antifungal activity of these isolates were also investigated. The results showed that compositacin G exhibited good antifungal activity against Microsporum gypseum (Cmccfmza) with a MIC80 value of 4 µg/mL relative to positive controls. Four of the chamigrane halosesquiterpenoids showed marginal cytotoxicity against the A-549 human lung adenocarcinoma cell line with IC50 values ranging from 48.6 to 85.2 µM.

Lysophospholipids from the Guangxi Sponge Spirastrella purpurea.

Four known (1-4) and two new (5 and 6) lysophospholipids were isolated from the sponge Spirastrella purpurea from Weizhou Island, Guangxi Autonomous Region, China. The structures of the new compounds (5 and 6) were elucidated by detailed spectroscopic techniques, including 1D and 2D NMR ((1)H and (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments. The known compounds (1-4) were identified by comparison of their spectroscopic data and specific optical rotation with those reported in the literature. The isolated compounds displayed various moderate in vitro antifungal activities against four fungi (Cryptococcus neoformans, Candida glabrata, Trichophyton rubrum, and Aspergillus fumigatus), whereas they displayed no neuroprotective activity against Aß25-35-induced SH-SY5Y cell damage.

A novel citrinin derivative from the marine-source fungus Penicillium citrinum.

A novel citrinin derivative, penicitrinol L (1), along with two known analogues, penidicitrinin B (2) and pennicitrinone A (3) were isolated from the marine-source fungus Penicillium citrinum. The structure of the new compound was elucidated by spectroscopic methods including one and two-dimensional NMR as well as high-resolution mass spectrometric analysis. Furthermore, compound 1 showed modest cytotoxic activity against HL-60 cell line and compound 3 showed weak cytotoxic activity against A375 cell line.

Bioactive constituents from the green alga Caulerpa racemosa.

Three diterpenoids, including a pair of epimers, racemobutenolids A and B (1 and 2), and 4',5'-dehydrodiodictyonema A (3), an α-tocopheroid, α-tocoxylenoxy (8), and an 28-oxostigmastane steroid, (23E)-3ß-hydroxy-stigmasta-5,23-dien-28-one (11), together with 12 known compounds, were isolated from the green alga Caulerpa racemosa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. The epimers (1 and 2) are two unusual diterpenoid lactones bearing a ß-methyl-γ-substituted butenolide moiety, and 3 and 8 represent the first naturally occurring natural products with a hematinic acid ester group and 3,5-dimethylphenoxy functionality, respectively. The enzyme inhibitory activities of the isolated compounds were evaluated in vitro against PTP1B and related PTPs (TCPTP, CDC25B, LAR, SHP-1, and SHP-2). Compounds 3, 5, 6, and 9-14 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 2.30 to 50.02µM. Of these compounds, 3, 9, and 11 showed the most potent inhibitory activities towards PTP1B with IC50 values of 2.30, 3.85, and 3.80µM, respectively. More importantly, the potent PTP1B inhibitors 3, 9, and 11 also displayed high selectivity over the highly homologous TCPTP and other PTPs. Also, the neuroprotective effects of the isolates against Aß25-35-induced cell damage in SH-SY5Y cells were investigated. Compounds 10, 11, and 14 exhibited significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell damage with 11.31-15.98% increases in cell viability at 10µM. In addition, the cytotoxic activities of the isolated compounds were tested against the human cancer cell lines A-549 and HL-60.

Racemosin C, a novel minor bisindole alkaloid with protein tyrosine phosphatase-1B inhibitory activity from the green alga Caulerpa racemosa.

A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC50 values of 5.86 ± 0.57 and 7.14 ± 1.00 µM, respectively, compared with the positive control oleanolic acid (IC50 = 3.03 ± 0.20 µM). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors.

New isoquinolinequinone alkaloids from the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp.

Two new renieramycin-type bistetrahydroisoquinolinequinone alkaloids, fennebricins A (1) and B (5), and one new isoquinolinequinone alkaloid, N-formyl-1,2-dihydrorenierol (7), were isolated from the skin of the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp., together with eight known metabolites, including three bistetrahydroisoquinolinequinones (2-4) and five isoquinolinequinones (8-12). Their structures were elucidated by analysis of spectroscopic data including 1D and 2D NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS) and by comparison with data for related known compounds. All the metabolites except for 7 occurred simultaneously in the two animals, supporting recent ecological studies that the nudibranch J. funebris preys on the sponge of the genus Xestospongia.

A seco-laurane sesquiterpene and related laurane derivatives from the red alga Laurencia okamurai Yamada.

A ring-cleaved sesquiterpene, named seco-laurokamurone, four laurane-type sesquiterpenes, laurepoxyene, 3ß-hydroperoxyaplysin, 3α-hydroperoxy-3-epiaplysin, and 8,10-dibromoisoaplysin, one laurokamurane-type sesquiterpene, laurokamurene D, and one bisabolane-type sesquiterpene, (5S)-5-acetoxy-ß-bisabolene, have been isolated from a re-collection of the red alga Laurencia okamurai Yamada, together with six other known sesquiterpenes. Their structures, including relative configuration, were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. In addition, on the basis of chemical conversions, degradation results, and biogenetic considerations, the absolute configurations of several of these compounds were also tentatively proposed. seco-Laurokamurone possesses an unprecedented carbon skeleton, formed from an oxidative cleavage of the laurokamurane skeleton, and laurokamurene D represents the fourth example of a laurokamurane-type sesquiterpene from a natural source. The in vitro antifungal activity of many of these compounds was evaluated against four fungi (Cryptococcus neoformans, Candida glabrata, Trichophyton rubrum, and Aspergillus fumigatus), as well as assessing cytotoxicity against HL-60 and A-549 human cancer cell lines. The compounds studied displayed moderate activities, relative to controls.