New Briarane Diterpenoids from Taiwanese Soft Coral Briareum violacea

Ten new briarane diterpenoids, briaviolides A–J (1–10), together with six known briaranes, solenolides A and D, excavatolide A, briaexcavatolide I, 4β-acetoxy-9-deacetystylatulide lactone and 9-deacetylstylatulide lactone, were isolated from the Taiwanese soft coral, Briareum violacea. Their structures were determined on the basis of spectroscopic data (¹H- and ¹³C-NMR, ¹H–¹H COSY, HSQC, HMBC and NOESY), HR-MS and chemical methods. The absolute configuration of briaviolide A (1) was determined by X-ray crystallographic analysis. Compounds 5, 9 and derivative 11 showed moderate inhibitory activities on superoxide-anion generation and elastase release by human neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine/Cytochalasin B (fMLP/CB).     

Preparation,chemical, and thermal characterization of nylon 4/6 copolymers by anionic ring opening polymerization of 2-Pyrrolidone and ε-Caprolactam

Nylon 4/6 copolymers based on 2-pyrrolidone (C4) and ε-caprolactam (C6) were synthesized and characterized as part of ongoing efforts to develop thermally stable, melt-processable 2-pyrrolidone (C4) based Nylons. Copolymers of various compositions were synthesized at between 50 and 100 °C via the anionic ring opening polymerization of C4 and C6 using a potassium tert-butoxide catalyst and a benzoyl chloride initiator. The polymers were characterized by NMR spectroscopy, DSC, TGA, GPC, intrinsic viscosity measurements, and X-ray scattering (SAXS and WAXS). Their chemical compositions and sequence distributions were obtained by ¹H- and ¹³C-NMR spectroscopies, respectively. X-ray scattering was used to investigate the lamellar morphologies and the crystal structures of solvent cast films of the copolymers. WAXS revealed the presence of α-phase crystals in the copolymers. TGA data coupled with molecular weight and sequence distribution information indicated that the polymers’ thermal stability depended on both their chemical composition and their sequence distribution.     

Identification and Bioactivity of Compounds from the Mangrove Endophytic Fungus Alternaria sp.

Racemic new cyclohexenone and cyclopentenone derivatives, (±)-(4R*,5S*,6S*)-3-amino-4,5,6-trihydroxy-2-methoxy-5-methyl-2-cyclohexen-1-one (1) and (±)-(4S*,5S*)-2,4,5-trihydroxy-3-methoxy-4-methoxycarbonyl-5-methyl-2-cyclopenten-1-one (2), and two new xanthone derivatives 4-chloro-1,5-dihydroxy-3-hydroxymethyl-6-methoxycarbonyl-xanthen-9-one (3) and 2,8-dimethoxy-1,6-dimethoxycarbonyl-xanthen-9-one (4), along with one known compound, fischexanthone (5), were isolated from the culture of the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS (Mass), one and two dimensional NMR (nuclear magnetic resonance) spectroscopic data. Compounds 1 and 2 exhibited potent ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] scavenging activities with EC₅₀ values of 8.19 ± 0.15 and 16.09 ± 0.01 μM, respectively. In comparison to Triadimefon, compounds 2 and 3 exhibited inhibitory activities against Fusarium graminearum with minimal inhibitory concentration (MIC) values of 215.52 and 107.14 μM, respectively, and compound 3 exhibited antifungal activity against Calletotrichum musae with MIC value of 214.29 μM.     

Structure Elucidation and in Vitro Toxicity of New Azaspiracids Isolated from the Marine Dinoflagellate Azadinium poporum

Two strains of Azadinium poporum, one from the Korean West coast and the other from the North Sea, were mass cultured for isolation of new azaspiracids. Approximately 0.9 mg of pure AZA-36 (1) and 1.3 mg of pure AZA-37 (2) were isolated from the Korean (870 L) and North Sea (120 L) strains, respectively. The structures were determined to be 3-hydroxy-8-methyl-39-demethyl-azaspiracid-1 (1) and 3-hydroxy-7,8-dihydro-39-demethyl-azaspiracid-1 (2) by ¹H- and ¹³C-NMR. Using the Jurkat T lymphocyte cell toxicity assay, (1) and (2) were found to be 6- and 3-fold less toxic than AZA-1, respectively.     

Tedaniophorbasins A and B—Novel Fluorescent Pteridine Alkaloids Incorporating a Thiomorpholine from the Sponge Tedaniophorbas ceratosis

Two new fluorescent pteridine alkaloids, tedaniophorbasins A (1) and B (2), together with the known alkaloid N-methyltryptamine, were isolated, through application of mass directed purification, from the sponge Tedaniophorbas ceratosis collected from northern New South Wales, Australia. The structures of tedaniophorbasins A and B were deduced from the analysis of 1D/2D NMR and MS data and through application of ¹³C NMR DFT calculations. Tedaniophorbasin A possesses a novel 2-imino-1,3-dimethyl-2,3,7,8-tetrahydro-1H-[1,4]thiazino[3,2-g]pteridin-4(6H)-one skeleton, while tedaniophorbasin B is its 2-oxo derivative. The compounds show significant Stokes shifts (~14,000 cm⁻¹) between excitation and emission wavelengths in their fluorescence spectra. The new compounds were tested for bioactivity against chloroquine-sensitive and chloroquine-resistant strains of the malaria parasite Plasmodium falciparum, breast and pancreatic cancer cell lines, and the protozoan parasite Trypanosoma brucei brucei but were inactive against all targets at 40 µM.     

Structural differences between non-wood plant celluloses: evidence from solid state NMR,vibrational spectroscopy and X-ray diffractometry

Cellulose from flax, hemp, kenaf and sorghum was investigated by solid state NMR and vibrational spectroscopy, and the structural differences found were validated by X-ray diffractometry. All three techniques indicate a notable region of order in the cellulose of both flax and hemp, but the absolute crystallinity values are not directly comparable. CP-MAS ¹³C-NMR and FTIR spectroscopy revealed the presence of Iα and Iβ forms in all the samples. On passing from flax and hemp to kenaf and sorghum the progressive loss in the crystalline phase is evidenced by ¹³C-CPMAS T₁ measurements; ¹H-CPMAS T_1ρ measurement revealed an analogous loss in phase dimension for the ordered phase, but similar dimension values for the paracrystalline and amorphous phases. The FTIR and FTRaman spectra of all the cellulose samples reveal the same chain conformation but a different hydrogen bond pattern, and this accounts for the NMR and X-ray results.     

Five New Cytotoxic Metabolites from the Marine Fungus Neosartorya pseudofischeri

The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 1–11 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda.     

Bioactive Secondary Metabolites from the Red Sea Marine Verongid Sponge Suberea Species

In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (¹H and ¹³C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC₅₀ values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC₅₀ of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds.     

Hyaluromycin,a New Hyaluronidase Inhibitor of Polyketide Origin from Marine Streptomyces sp.

Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the interpretation of NMR data for the compound and its 3″-O-methyl derivative in combination with an incorporation experiment with [1,2-¹³C₂]acetate. The compound’s absolute configuration was determined by the comparison of its circular dichroism (CD) spectrum with those of other rubromycins. Hyaluromycin (1) consists of a γ-rubromycin core structure possessing a 2-amino-3-hydroxycyclopent-2-enone (C₅N) unit as an amide substituent of the carboxyl function; both structural units have been reported only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more potent hyaluronidase inhibitory activity against hyaluronidase than did glycyrrhizin, a known inhibitor of plant origin.     

1-O-Alkylglycerol Ethers from the Marine Sponge Guitarra abbotti and Their Cytotoxic Activity

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge Guitarra abbotti, whose 1-O-alkyl-sn-glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using ¹H and ¹³C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1-O-(Z-docos-15-enyl)-sn-glycerol (1), 1-O-(Z-docos-17-enyl)-sn-glycerol (2), 1-O-(Z-tricos-15-enyl)-sn-glycerol (3), 1-O-(Z-tricos-16-enyl)-sn-glycerol (4), 1-O-(Z-tricos-17-enyl)-sn-glycerol (5), and 1-O-(Z-tetracos-15-enyl)-sn-glycerol (6). The isolated AGEs show weak cytotoxic activity in THP-1, HL-60, HeLa, DLD-1, SNU C4, SK-MEL-28, and MDA-MB-231 human cancer cells. A further cytotoxicity analysis in JB6 P⁺ Cl41 cells bearing mutated MAP kinase genes revealed that ERK2 and JNK1 play a cytoprotective role in the cellular response to the AGE-induced cytotoxic effects.     

Dermacozine N,the First Natural Linear Pentacyclic Oxazinophenazine with UV–Vis Absorption Maxima in the Near Infrared Region,along with Dermacozines O and P Isolated from the Mariana Trench Sediment Strain Dermacoccus abyssi MT 1.1T

Three dermacozines, dermacozines N–P (1–3), were isolated from the piezotolerant Actinomycete strain Dermacoccus abyssi MT 1.1^T, which was isolated from a Mariana Trench sediment in 2006. Herein, we report the elucidation of their structures using a combination of 1D/2D NMR, LC-HRESI-MSⁿ, UV–Visible, and IR spectroscopy. Further confirmation of the structures was achieved through the analysis of data from density functional theory (DFT)–UV–Visible spectral calculations and statistical analysis such as two tailed t-test, linear regression-, and multiple linear regression analysis applied to either solely experimental or to experimental and calculated ¹³C-NMR chemical shift data. Dermacozine N (1) bears a novel linear pentacyclic phenoxazine framework that has never been reported as a natural product. Dermacozine O (2) is a constitutional isomer of the known dermacozine F while dermacozine P (3) is 8-benzoyl-6-carbamoylphenazine-1-carboxylic acid. Dermacozine N (1) is unique among phenoxazines due to its near infrared (NIR) absorption maxima, which would make this compound an excellent candidate for research in biosensing chemistry, photodynamic therapy (PDT), opto-electronic applications, and metabolic mapping at the cellular level. Furthermore, dermacozine N (1) possesses weak cytotoxic activity against melanoma (A2058) and hepatocellular carcinoma cells (HepG2) with IC₅₀ values of 51 and 38 μM, respectively.     

New Antiproliferative Compounds against Glioma Cells from the Marine-Sourced Fungus Penicillium sp. ZZ1750

Seven novel compounds, namely peniresorcinosides A–E (1–5), penidifarnesylin A (6), and penipyridinone A (7), together with the 11 known ones 8–17, were isolated from a culture of the marine-associated fungus Penicillium sp. ZZ1750 in rice medium. The structures of the new compounds were established based on their high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, extensive nuclear magnetic resonance (NMR) spectroscopic analyses, chemical degradation, Mosher’s method, ¹³C-NMR calculations, electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Peniresorcinosides A (1) and B (2) are rare glycosylated alkylresorcinols and exhibited potent antiglioma activity, with IC₅₀ values of 4.0 and 5.6 µM for U87MG cells and 14.1 and 9.8 µM for U251 cells, respectively.     

New α-Glucosidase Inhibitory Triterpenic Acid from Marine Macro Green Alga Codium dwarkense Boergs

The marine ecosystem has been a key resource for secondary metabolites with promising biological roles. In the current study, bioassay-guided phytochemical investigations were carried out to assess the presence of enzyme inhibitory chemical constituents from the methanolic extract of marine green alga—Codium dwarkense. The bioactive fractions were further subjected to chromatographic separations, which resulted in the isolation of a new triterpenic acid; dwarkenoic acid (1) and the known sterols; androst-5-en-3β-ol (2), stigmasta-5,25-dien-3β,7α-diol (3), ergosta-5,25-dien-3β-ol (4), 7-hydroxystigmasta-4,25-dien-3-one-7-O-β-d-fucopyranoside (5), 7-hydroxystigmasta-4,25-dien-3-one (6), and stigmasta-5,25-dien-3β-ol (7). The structure elucidation of the new compound was carried out by combined mass spectrometry and 1D (¹H and ¹³C) and 2D (HSQC, HMBC, COSY, and NOESY) NMR spectroscopic data. The sub-fractions and pure constituents were assayed for enzymatic inhibition of alpha-glucosidase. Compound 1 showed significant inhibition at all concentrations. Compounds 2, 3, 5, and 7 exhibited a dose-dependent response, whereas compounds 4–6 showed moderate inhibition. Utilizing such marine-derived biological resources could lead to drug discoveries related to anti-diabetics.     

Identification and Bioactivity of Compounds from the Fungus Penicillium sp. CYE-87 Isolated from a Marine Tunicate

In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1), tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) and terretrione C (6), were isolated from Penicillium sp. CYE-87. The structures of the isolated compounds were established by spectral analysis, including 1D (¹H, ¹³C) and 2D (COSY, multiplicity edited-HSQC and HMBC) NMR and HRESIMS, as well as comparison of their NMR data with those in the literature. The compounds were evaluated for their antimigratory activity against the human breast cancer cell line (MDA-MB-231) and their antiproliferation activity against HeLa cells. Compounds 2 and 6 showed significant antimigratory activity against MDA-MB-231, as well as antifungal activity against C. albicans.     

A Series of New Pyrrole Alkaloids with ALR2 Inhibitory Activities from the Sponge Stylissa massa

Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge Stylissa massa collected in the South China Sea. Compound 1 is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds 2–5 and 13–15 belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). Z- and E-configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of ¹³C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds 1, 5, and 10. In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds (2–5, 13–15) displayed significant activities. Compounds 13 and 14, as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with K_D values of 12.5 and 6.9 µM, respectively.     

New Prenylxanthones from the Deep-Sea Derived Fungus Emericella sp. SCSIO 05240

Four new prenylxanthones, emerixanthones A–D (1–4), together with six known analogues (5–10), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology and ITS sequence analysis. The newstructures were determined by NMR (¹H, ¹³C NMR, HSQC, HMBC, and ¹H-¹H COSY), MS, CD, and optical rotation analysis. The absolute configuration of prenylxanthone skeleton was also confirmed by the X-ray crystallographic analysis. Compounds 1 and 3 showed weak antibacterial activities, and 4 displayed mild antifungal activities against agricultural pathogens.     

Synthesis,spectral characterization of azo dyes derived from calix[4]resorcinarene and their application in dyeing of fibers

Seven new upper rim functionalized azocalix[4]resorcinarene dyes have been synthesized by coupling calix[4]resorcinarene with different diazo compounds of p-chloroaniline, p-nitroaniline, p-toludine, p-anisidine, p-aminobenzoic acid, o-aminophenol, and aniline. The characterization of these dyes has been carried out by elemental analysis, FT-IR, ¹H- and ¹³C-NMR. Effect of solvents of varying dielectric constants on the absorption spectra of substituted and unsubstituted azocalix[4]resorcinarene dyes have been examined by UV-vis spectrophotometer. These azocalix[4]resorcinarene dyes have also been used for dyeing textile fibers like cotton, silk, and wool. Their dyeing and fastness properties have also been discussed.     

13-Epi-9-deacetoxyxenicin,a Cytotoxic Diterpene from the Soft Coral Asterospicularia laurae (Alcyonacea)

An investigation of the soft coral Asterospicularia laurae collected on the Great Barrier Reef, Australia, afforded the cytotoxic diterpene 13-epi-9-deacetoxyxenicin (1) in addition to the known metabolites 13-epi-9-deacetylxenicin (2) and gorgosterol. 13-Epi-9-deacetoxyxenicin readily underwent an autoxidation reaction in solution to afford a single product, the hydroperoxide 3. Structures, stereochemistry, and NMR assignments were established by high resolution NMR spectroscopy and by comparison with published data for known compounds.     

New Monoterpenoids and Polyketides from the Deep-Sea Sediment-Derived Fungus Aspergillus sydowii MCCC 3A00324

Chemical study of the secondary metabolites of a deep-sea-derived fungus Aspergillus sydowii MCCC 3A00324 led to the isolation of eleven compounds (1–11), including one novel (1) and one new (2) osmane-related monoterpenoids and two undescribed polyketides (3 and 4). The structures of the metabolites were determined by comprehensive analyses of the NMR and HRESIMS spectra, in association with quantum chemical calculations of the ¹³C NMR, ECD, and specific rotation data for the configurational assignment. Compound 1 possessed a novel monoterpenoid skeleton, biogenetically probably derived from the osmane-type monoperpenoid after the cyclopentane ring cleavage and oxidation reactions. Additionally, compound 3 was the first example of the α-pyrone derivatives bearing two phenyl units at C-3 and C-5, respectively. The anti-inflammatory activities of 1–11 were tested. As a result, compound 6 showed potent inhibitory nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells with an inhibition rate of 94.4% at the concentration of 10 µM. In addition, a plausible biosynthetic pathway for 1 and 2 was also proposed.     

New Isocoumarin Analogues from the Marine-Derived Fungus Paraphoma sp. CUGBMF180003

Nine new secondary metabolites, including six isocoumarin analogues, 7-hydroxyoospolactone (1), 7-methoxyoospolactone (2), 7-methoxy-9-hydroxyoospolactone (3), 10-acetoxy-9-hydroxyoospolactone (4), 6-dehydroxysescandelin (5), parapholactone (6), and three compounds with a rare skeleton of isocoumarin coupled with phenylethylamine, namely paraphamide A (12), paraphamide B (13), and paraphamide C (14), together with five known compounds, oospolactone (7), 8-O-methyloospolactone (8), 10-hydroxyoospolactone (9), 9,10-dihydroxyoospolactone (10), and oospoglycol (11), were isolated and identified from the marine-derived fungus Paraphoma sp. CUGBMF180003. Their chemical structures were determined using spectroscopic data, including HRESIMS and 1D and 2D NMR techniques. Furthermore, the stereogenic carbons in 5 and 14 were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. The carbon skeleton of 12–14 was identified as the first example of isocoumarin coupled with phenylethylamine derivatives. All of these compounds were examined for antimicrobial activities against Candida albicans and Staphylococcus aureus. Both 1 and 6 showed antibacterial activity against S. aureus with MIC values of 12.5 μg/mL.