Novel Furanyl-Substituted Isochromanyl Class of Anti-Inflammatory Turbinochromanone from Brown Seaweed Turbinaria conoides.

Organic extract of the brown seaweed Turbinaria conoides (Sargassaceae) was chromatographically fractionated to yield an undescribed furanyl-substituted isochromanyl metabolite, named as turbinochromanone, which was characterized as methyl 4-[(3S)-8-{[(3R)-4-ethyl-2,3-dihydrofuran-3-yl]methyl}-1-oxo-3,4-dihydro-1H-2-benzopyran-3-yl]butanoate. The isochromanyl derivative possessed comparable attenuation potential against 5-lipoxygenase (IC50 3.70 µM) with standard 5-lipoxygenase inhibitor drug zileuton (IC50 2.41 µM). Noticeably, the index of anti-inflammatory selectivity of turbinochromanone (∼1.7) was considerably greater than that exhibited by the standard agent diclofenac (1.06). Antioxidant properties of turbinochromanone against oxidants (IC50 ∼24 µM) further supported its potential anti-inflammatory property. Greater electronic properties (topological polar surface area of 61.8) along with comparatively lesser docking parameters of the studied compound with aminoacyl residues of targeted enzymes (cyclooxygenase-2 and 5-lipoxygenase) (binding energy of -11.05 and -9.40 kcal mol-1 , respectively) recognized its prospective anti-inflammatory potential. In an aim to develop seaweed-based natural anti-inflammatory leads, the present study isolated turbinochromanone as promising 5-lipoxygenase and cyclooxygenase-2 inhibitor, which could be used for pharmaceutical and biotechnological applications.

Penicisteckins A-F, Isochroman-Derived Atropisomeric Dimers from Penicillium steckii HNNU-5B18.

Penicisteckins A-D (1-4), two pairs of atropodiastereomeric biaryl-type hetero- and homodimeric bis-isochromans with 7,5'- and 7,7'-linkages and a pair of atropodiastereomeric 2-(isochroman-5-yl)-1,4-benzoquinone derivatives [penicisteckins E (5) and F (6)], were isolated from the Penicillium steckii HNNU-5B18. Their structures including the absolute configuration were determined by extensive spectroscopic and single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Both the bis-isochromans and the isochroman/1,4-benzoquinone conjugates represent novel biaryl scaffolds containing both central and axial chirality elements. The monomer anserinone B (8) exhibited potent antibacterial activities against Staphylococcus aureus ATCC 29213 and methicillin-resistant Staphylococcus aureus with minimal inhibition concentration values ranging from 2 to 8 µg mL-1. Plausible biosynthetic pathways of 1-6 are proposed, which suggest how the absolute configurations of the isolates were established during the biosynthetic scheme.

Seven chromanoid norbisabolane derivatives from the marine-alga-endophytic fungus Trichoderma asperellum A-YMD-9-2.

An examination of the endophytic fungus Trichoderma asperellum A-YMD-9-2 obtained from the marine red alga Gracilaria verrucosa led to the isolation of seven new chromanoid norbisabolane derivatives, trichobisabolins I-L (1-4) and trichaspsides C-E (5-7). Their structures and relative configurations were established on the basis of spectroscopic techniques, mainly including 1D/2D NMR and MS, and the absolute configuration of 1 was assigned by X-ray crystallographic analysis using Cu Kα radiation. All of these isolates feature a 1,9-epoxy ring system, and 5-7 represent the second occurrence of norbisabolane aminoglycosides. Compounds 1-7 exhibited potent inhibition of several marine phytoplankton species.

Chromane Enantiomers from the Flower Buds of Tussilago farfara L. and Assignments of Their Absolute Configurations.

Fourteen chromane derivatives of seven pairs of enantiomers (1-14) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α-glucosidase inhibitory activities.

Isochromanes from Aspergillus fumigatus, an endophytic fungus from Cordyceps sinensis.

Four previously undescribed isochromanes were isolated from the fermentation broth of an endophytic fungus Aspergillus fumigatus, which was obtained from the fruiting body of Cordyceps sinensis. Their structures were elucidated through extensive spectroscopic analyses. One racemic isochromane was further purified by chiral HPLC to yield a pair of enantiomers and their absolute configurations were determined by quantum chemical ECD calculations. These isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-ME-231) and the result showed that compounds 1a and 2 exhibited moderate growth inhibition against MV4-11 cell line.

Isolation and Identification of Benzochroman and Acylglycerols from Massa Medicata Fermentata and Their Inhibitory Effects on LPS-Stimulated Cytokine Production in Bone Marrow-Derived Dendritic Cells.

Massa Medicata Fermentata (MMF), known as Shenqu, is an important traditional Chinese medicine widely used to treat indigestion, vomiting, and diarrhea. In this study, a new benzochroman, 3(S)-3,4-dihydro-5,10-di-ß-d-glucopyranoside-2,2-dimethyl-2H-naphtho(2,3-b)pyran-3-ol (1), and five known galactosyl acylglycerols (2⁻6) were isolated from a methanol extract from MMF. In addition, their chemical structures were determined by chemical and spectroscopic methods, which were compared with the previously reported data. Furthermore, the effects of isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 1⁻3 exhibited significant inhibitory effects on the LPS-induced production of IL-6 and IL-12 p40, with IC50 values ranging from 1.6 to 10.2 µM. Compounds 2 and 3 also exhibited strong inhibitory effects on the LPS-stimulated production of TNF-α with IC50 values of 12.0 and 11.2 µM, respectively. The results might provide a scientific basis for the development of the active components in MMF, as well as for novel anti-inflammatory agents.

Banksialactones and Banksiamarins: Isochromanones and Isocoumarins from an Australian Fungus, Aspergillus banksianus.

Chemical investigation of an Australian fungus, Aspergillus banksianus, led to the isolation of the major metabolite banksialactone A (1), eight new isochromanones, banksialactones B-I (2-9), two new isocoumarins, banksiamarins A and B (10 and 11), and the reported compounds, clearanol I (12), dothideomynone A (13), questin (14), and endocrocin (15). The structures of 1-11 were established by NMR spectroscopic data analysis, and the absolute configurations were determined from optical rotations and ECD spectra in conjunction with TD-DFT calculations. The secondary metabolite profile of A. banksianus is unusual, with the 11 most abundant metabolites belonging to a single isochromanone class. Conjugation of 1 with endocrocin, 5-methylorsellinic acid, 3,5-dimethylorsellinic acid, mercaptolactic acid, and an unknown methylthio source gave rise to five unprecedented biosynthetic hybrids, 5-9. The isolated compounds were tested for cytotoxicity, antibacterial, and antifungal activities, with hybrid metabolites 7-9 displaying weak cytotoxic and antibiotic activities.

New chromane and chromene meroterpenoids from flowers of Rhododendron rubiginosum Franch. var. rubiginosum.

Six new chromane and chromene meroterpenoids rubiginosins A-F (1-2, and 4-7), together with three known ones, rubiginosin G (3) and anthopogochromenes A and B (8-9),were isolated from the flowers of Rhododendron rubiginosum Franch. var. rubiginosum. Among them, 1-4 were the chromane ones derived from an intramolecular [2 + 2] cycloaddition of their respective chromene precursors, making a 6/6/6/4- or 6/6/5/4-ring fused scaffold. The absolute configuration of the chiral center at C-2 of 1-9 was determined as S by chromane/chromene helicity rule and X-ray crystallograph. Notably, more attention should be paid to 6-carboxyl derivatives, since the 6-carboxyl derivatives showed an abnormal diagnostic Cotton effect (CE) with respect to their normal diagnostic CE. Compounds 1-9 were tested for cytotoxicity against four cell lines (A549, HCT116, SK-HEP-1, and HL-60), and only 1, 3, 5, and 9 showed moderate cytotoxicity, while others were inactive, discovering the 6-carboxyl is crucial for their low cytotoxicity.

Caloinophyllin A, a new chromanone derivative from Calophyllum inophyllum roots.

A new chromanone derivative, namely caloinophyllin A (1), along with eight known compounds (2-9), nobiletin (2), pentamethylquercetin (3), 3,5,7,4'-tetramethoxyflavone (4), 5,7,4'-trimethoxyflavone (5), 1,5-dihydroxyxanthone (6), 1,8-dimethoxy-2-hydroxyxanthone (7), 1,6-dihydroxy-7-methoxyxanthone (8) and 4-methoxycaffeic acid (9) were isolated from the roots of Calophyllum inophyllum. The structures of all the isolated compounds (1-9) were fully characterised using spectroscopic data, as well as comparison with the previous literature data. In addition, the quantum chemical calculation has been used to confirm the conformation of 1. Moreover, all isolated compounds were assessed for their in vitro cytotoxicity against five human cancer cell lines.

The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil.

There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T1), α-tocotrienol (α-T3), γ-tocotrienol (γ-T3), ß-tocotrioenol (ß-T3) and δ-tocotrienol (δ-T3). These analogs were difficult to separate chromatographically due to their similar structures, physical and chemical properties. This paper reports on the effect of pressure and injection solvent on the separation of the tocol analogs in palm oil. Supercritical CO2 modified with ethanol was used as the mobile phase. Both total elution time and resolution of the tocol analogs decreased with increased pressure. Ethanol as an injection solvent resulted in peak broadening of the analogs within the entire pressure range studied. Solvents with an eluent strength of 3.4 or less were more suitable for use as injecting solvents.

Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy. AIM OF THE STUDY: The aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species. RESULTS: significantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats. CONCLUSION: Thus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

[Novel biocatalyst for productions of S-(-)-2-[6-benzyloxy -2,5,7,8-tetramethylchroman -2-yl] ethanol­precursor of natural α-tocols].

A novel promising strain of actinobacteria Rhodococcus sp. 77-32 was identified. Its acetonetreated biomass the could be used as a biocatalyst for production of S-(-)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl] ethanol (S-BCE), a precursor of natural α-tocols. It was established that a reaction of enantioselective hydrolysis of racemic (±)-2-(2-acetoxyethyl)-6-benzyloxy-2,5,7,8-tetramethylchroman (BCEA) occurred in the phosphate buffer­acetone system, resulting in enrichment of the residual substrate by S-enantiomer (S-(+)-2-(2-acetoxyethyl)-6-benzyloxy-2,5,7,8-tetramethylchroman, S-BCEA). It was shown that the hydrolysis was accompanied by stereoinversion of the formed product, R-(+)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl] ethanol (R-BCE), into the S-BCE. The transformation conditions (acetone content, acidity, temperature, reaction duration) were optimized, providing simultaneous production of optically pure S-BCE and S-BCEA with an almost quantitative yield.

Isochromans and Related Constituents from the Endophytic Fungus Annulohypoxylon truncatum of Zizania caduciflora and Their Anti-Inflammatory Effects.

Six new isochroman derivatives (annulohypoxylomans A-C, 1-3; annulohypoxylomanols A and B, 6 and 7; and annulohypoxyloside, 8), an isocoumarin (annulohypoxylomarin A, 4), and an azaphilone derivative (xylariphilone, 5) were isolated from an ethyl acetate extract derived from cultures of the endophytic fungus JS540 found in the leaves of Zizania caduciflora. The JS540 strain was identified as Annulohypoxylon truncatum. The structures of the isolated compounds were elucidated by one- and two-dimensional nuclear magnetic resonance and mass spectrometry and by comparison with related compounds from the literature. The anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Xylariphilone (5) exhibited significant inhibitory effects on LPS-induced interleukin (IL)-6, IL-12 p40, and tumor necrosis factor (TNF)-α production with IC50 values of 5.3, 19.4, and 37.6 µM, respectively.

Novel Isochroman Dimers from Stachybotrys sp. PH30583: Fermentation, Isolation, Structural Elucidation and Biological Activities.

The rare anishidiol and five new isochromans, including three novel dimers with unprecedented skeletons, were isolated from Stachybotrys sp. PH30583. Their structures were determined by spectral analyses. The bioactivities of these compounds were also investigated. The dimers (6-10) inhibited acetylcholinesterase at 50 µM, but the monomers did not. To investigate the biogenesis of the novel dimers, a time-course investigation of metabolite production was undertaken.

Chemical constituents and their antibacterial activity from the tropical endophytic fungus Diaporthe sp. F2934.

AIMS: To isolate, characterize and determine the antibacterial activities of compounds produced by the endophytic fungus Diaporthe sp. F2934, cultivated on malt extract agar. METHODS AND RESULTS: The fungus was cultivated aseptically in Petri dishes containing malt extract agar at 25°C for 15 days. Crude extract was obtained from mycelium using ethyl acetate and sonication, and was fractioned using classic chromatography and HPLC. The structures of phomosines and chromanones were established by NMR experiments including HMQC, HMBC and COSY. Their molecular formulas were determined by ESI-TOFMS. We obtained six compounds: (1) 4H-1-benzopyra-4-one-2,3-dihydro-5-hydroxy-2,8-dimetyl, (2) 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxylmethyl)-2-methyl, (3) 4H-1-benzopyra-4-one-2,3-dihydro-5-methoxyl-2,8-dimetyl, (4) phomosine A, (5) phomosine D and (6) phomosine C. Isolated compounds 1, 2 and 5 were inactive against 15 micro-organisms, but phomosines A and C were active against diverse Gram-negative and Gram-positive bacteria. CONCLUSIONS: A group of new chromanones and known phomosines have been isolated from the genus Diaporthe (Diaporthe sp. F2934). The results obtained confirm the wide chemical diversity produced by endophytic fungi, specifically the genus Diaporthe. In addition, phomosines A and C may be considered as antimicrobial agents that can be used to guide the development of new antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Our phylogenetic analysis places Diaporthe sp. F2934 as sister to the Diaporthe cynaroidis clade. Three chromanones were isolated and identified, for the first time, using crude extract obtained from Diaporthe F2934. From this extract phomosines A, C and D were also purified. Regarding Staphylococcus aureus, the inhibition zone diameter (IZD) for phomosine A was 20% higher than the standard drug, vancomycin. When cultivated as described here, Diaporthe sp. F2934 produced new and antimicrobial compounds.

Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum.

From the ethno-medicinally used leaves of Hypericum roeperianum we isolated a new tricyclic acylphloroglucinol (1), a new tetracyclic acylphloroglucinol (2), and a new prenylated bicyclic acylphloroglucinol (3) together with four known prenylated (4-7) and three known tetracyclic acylphloroglucinol derivatives (8-10). Structure elucidation was based on UV, IR, [α]D(25), 1D- and 2D-NMR experiments. Furthermore, empetrifranzinans A (8) and C (9) were synthesized regioselectively in only two steps. The isolated compounds were evaluated for their cytotoxicity against PC-3 and HT-29 cancer cell lines as well as antibacterial and anthelmintic activities. They were also tested in cell-based assays for cytotoxicity against MT-4 cells and for anti-HIV activity in infected MT-4 cells. Significant anthelmintic activity against Caenorhabditis elegans was exhibited by compound 7 (3-geranyl-1-(2'-methylbutanoyl)-phloroglucinol), which might provide a new lead.

Phytochemicals and Estrogen-Receptor Agonists from the Aerial Parts of Liriope platyphylla.

One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or ß as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.

Antimicrobial constituents from the flowers of Trollius chinensis.

A new 1-aryl-isochroman, trolliusol A (1), was isolated from the flowers of Trollius chinensis, along with seven known phenolic compounds in an antimicrobial activity-directed phytochemical investigation. The structures of these compounds were elucidated by spectroscopic methods, and their inhibitory activities against one fungus and four bacterial strains were measured.

Secondary metabolites from Penicillium corylophilum isolated from damp buildings.

Indoor exposure to the spores and mycelial fragments of fungi that grow on damp building materials can result in increased non-atopic asthma and upper respiratory disease. The mechanism appears to involve exposure to low doses of fungal metabolites. Penicillium corylophilum is surprisingly common in damp buildings in USA, Canada and western Europe. We examined isolates of P. corylophilum geographically distributed across Canada in the first comprehensive study of secondary metabolites of this fungus. The sesquiterpene phomenone, the meroterpenoids citreohybridonol and andrastin A, koninginin A, E and G, three new alpha pyrones and four new isochromans were identified from extracts of culture filtrates. This is the first report of koninginins, meroterpenoids and alpha pyrones from P. corylophilum. These secondary metabolite data support the removal of P. corylophilum from Penicillium section Citrina and suggest that further taxonomic studies are required on this species.

Isochromans and α-pyrones from Penicillium corylophilum.

Seven new secondary metabolites, four isochromans (1-4) and three α-pyrones (5-7), were isolated from Penicillium corylophilum DAOM 242293 collected from a damp building in Halifax, Canada. Their structures were elucidated by HRESIMS, 1D and 2D NMR, chemical derivatization, ORD, UV, and comparison to the literature. Related isochromans have previously been reported from other Penicillium species; however, to our knowledge this is the first report of α-pyrones from P. corylophilum. Compounds 1-4 demonstrated antifungal activity against Saccharomyces cerevisiae at 100 µg mL(-1).