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Three new 5,5,6,6,5-pentacyclic spongian diterpenes, spongenolactones A-C ( 1 - 3 ), were isolated from a Red Sea sponge Spongia sp. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configurations of 1- 3 were determined on the basis of comparison of the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. Compounds 1 - 3 are the first 5,5,6,6,5-pentacyclic spongian diterpenes bearing an β -hydroxy group at C-1. These metabolites were assayed for their cytotoxic, antibacterial, and anti-inflammatory activities. All three compounds were found to exert inhibitory activity against superoxide anion generation in fMLF/CB-stimulated human neutrophils. Furthermore, 1 showed a higher activity against the growth of Staphylococcus aureus in comparison to 2 .

A polyoxygenated and halogenated labdane, spongianol ( 1 ); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24 S -ethylcholest-7-en-6-one ( 2 ); a rare seven-membered lactone B ring, (22 E ,24 S )-ergosta-7,22-dien-3β,5α-diol-6,5-olide ( 3 ); and an α,β-unsaturated fatty acid, ( Z )-3-methyl-9-oxodec-2-enoic acid ( 4 ) as well as five known compounds, 10-hydroxykahukuene B ( 5 ), pacifenol ( 6 ), dysidamide ( 7 ), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester ( 8 ), and the primary metabolite 2'-deoxynucleoside thymidine ( 9 ), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum , and metabolites 5 and 6 , isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia . Compounds 1 - 9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.

The new asperorlactone ( 1 ), along with the known illudalane sesquiterpene echinolactone D ( 2 ), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2 H -pyran-2-one ( 3 ) and its acetate 4 , and 4-hydroxybenzaldehyde ( 5 ), were isolated from a culture of Aspergillus oryzae , collected from Red Sea marine sediments. The structure of asperorlactone ( 1 ) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone ( 1 ) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC 50 values < 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone ( 1 ), a carboxylic acid, spongiafuranic acid A ( 2 ), one hydroxamic acid, spongiafuranohydroxamic acid A ( 3 ), and a furanyl trinorsesterpenoid 16- epi -irciformonin G ( 4 ), along with three known metabolites (-)-sponalisolide B ( 5 ), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one ( 6 ), and cholesta-7-ene-3β,5α-diol-6-one ( 7 ). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N -formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F-L ( 1 - 7 ). The chemical structures of 1 - 7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1 - 7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N -formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G ( 2 ) and cherbonolide H ( 3 ) displayed a more active effect than others on the inhibition of elastase release (48.2% ± 6.2%) and superoxide anion generation (44.5% ± 4.6%) at 30 µM, respectively.

Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F-P ( 1 - 11 ) of lobane- and prenyleudesmane-types, along with two known metabolites ( 12 and 13 ). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher's method. The complete assignment of 1 H and 13 C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1 , 2 , 4 , 12 , and 13 . A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium .

Two new capnosane-based diterpenoids, flaccidenol A ( 1 ) and 7- epi -pavidolide D ( 2 ), two new cembranoids, flaccidodioxide ( 3 ) and flaccidodiol ( 4 ), and three known compounds 5 to 7 were characterized from the marine soft coral Klyxum flaccidum , collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus Klyxum for the first time. The cytotoxicity of compounds 1 to 7 against the proliferation of a limited panel of cancer cell lines was assayed. The isolated diterpenoids also exhibited anti-inflammatory activity through suppression of superoxide anion generation and elastase release in the N -formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-stimulated human neutrophils. Furthermore, 1 and 7 also exhibited cytotoxicity toward the tested cancer cells, and 7 could effectively inhibit elastase release. It is worth noting that the biological activities of 7 are reported for the first time in this paper., Competing Interests: The authors declare no conflicts of interest.

Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C ( 1 ‒ 3 ), were isolated from a Formosan gorgonian Briareum violaceum . The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The absolute configuration of 1 was further confirmed by a single crystal X-ray diffraction analysis. The in vitro cytotoxic and anti-inflammatory potentialities of the isolated metabolites were tested against the growth of a limited panel of cancer cell lines and against the production of superoxide anions and elastase release in N -formyl-methionyl-leucyl-phenyl-alanine and cytochalasin B (fMLF/CB)-stimulated human neutrophils, respectively.

Six new cembranoids, cherbonolides A-E ( 1 ⁻ 5 ) and bischerbolide peroxide ( 6 ), along with one known cembranoid, isosarcophine ( 7 ), were isolated from the Formosan soft coral Sarcophyton cherbonnieri . The structures of these compounds were elucidated by detailed spectroscopic analysis and chemical methods. Compound 6 was discovered to be the first example of a molecular skeleton formed from two cembranoids connected by a peroxide group. Compounds 1 ⁻ 7 were shown to have the ability of inhibiting the production of superoxide anions and elastase release in N -formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLF/CB)-induced human neutrophils.

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A⁻C ( 1 ⁻ 3 ), stellatumonins A and B ( 4 and 5 ), and stellatumonone ( 6 ), were isolated together with ten known related compounds ( 7 ⁻ 16 ) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum . The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells.

Three new polyoxygenated steroids, michosterols A-C ( 1 - 3 ), and four known compounds ( 4 - 7 ) were isolated from the ethyl acetate (EtOAc) extract of the soft coral Lobophytum michaelae , collected off the coast of Taitung. The structures of the new compounds were elucidated on the basis of spectroscopic analyses and comparison of the nuclear magnetic resonance (NMR) data with related steroids. The cytotoxicity of compounds 1 - 3 against the proliferation of a limited panel of cancer cell lines was assayed. Compound 1 was found to display moderate cytotoxicity against adenocarcinomic human alveolar basal epithelial (A549) cancer cells. It also exhibited potent anti-inflammatory activity by suppressing superoxide anion generation and elastase release in N -formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-stimulated human neutrophils. Furthermore, 3 could effectively inhibit elastase release, as well., Competing Interests: The authors declare no conflicts of interest.

New lobane-based diterpenoids lobovarols A-D ( 1 - 4 ) and a prenyleudesmane-type diterpenoid lobovarol E ( 5 ) along with seven known related diterpenoids ( 6 - 12 ) were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum varium . Their structures were identified on the basis of multiple spectroscopic analyses and spectral comparison. The absolute configuration at C-16 of the known compound 11 is reported herein for the first time. The anti-inflammatory activities of compounds 1 - 12 were assessed by measuring their inhibitory effect on N -formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils. Metabolites 2 , 5 , and 11 were found to show moderate inhibitory activity on the generation of superoxide anion, while compounds 5 , 8 , 11 , and 12 could effectively suppress elastase release in fMLP/CB-stimulated human neutrophil cells at 10 μM. All of the isolated diterpenoids did not exhibit cytotoxic activity (IC 50 > 50 μM) towards a limited panel of cancer cell lines., Competing Interests: The authors declare no conflict of interest.

Five new isoprenoids, 3,4,8,16-tetra- epi -lobocrasol ( 1 ), 1,15β-epoxy-deoxysarcophine ( 2 ), 3,4-dihydro-4α,7β,8α-trihydroxy-Δ²-sarcophine (3), ent -sarcophyolide E (4), and 16-deacetyl- halicrasterol B (5) and ten known compounds 6‒ 15 , were characterized from the marine soft coral Sarcophyton glaucum , collected off Taitung coastline. Their structures were defined by analyzing spectra data, especially 2D NMR and electronic circular dichroism (ECD). The structure of the known compound lobocrasol ( 7 ) was revised. Cytotoxicity potential of the isolated compounds was reported, too., Competing Interests: The authors declare no conflicts of interest.

New cembranoids klyflaccicembranols A-I ( 1 - 9 ), along with gibberosene D ( 10 ), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum . Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, and spectral data comparison with related structures. The cytotoxicity of the isolated metabolites, as well as their nitric oxide (NO) inhibitory activity, were evaluated and reported. Metabolites 2 , 4 , 6 , 8 and 9 were found to exhibit variable activities against a limited panel of cancer cell lines in a range of IC 50 16.5-49.4 μM. Among the tested cembranoids, compounds 4 , 5 , 6 , and 9 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages at a dose of 50 μg/mL., Competing Interests: The authors declare no conflict of interest.