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Four new natural chemical entities, including 2-hydroxy-α-truxillic acid ( 2 ), (3 R ,4 S )-2,2-dimethyl-3-hydroxy-4-(1-angeloyloxy)-6-acetyl-7-methoxychromane ( 3 ), N -tricosanoyltyramine ( 4 ), and grandifolamide ( 5 ), were isolated along with 11 known compounds ( 1 , 6 - 15 ) from the aerial parts of Ageratina grandifolia . The chemical structures were elucidated using chemical derivatization and HR-MS, NMR, and DFT-calculated chemical shifts, combined with DP4+ statistical analysis. It was found that 2 decomposed into its biogenetic precursor, o -coumaric acid, upon standing at room temperature for a few weeks. 3,5-Diprenyl-4-hydroxyacetophenone ( 8 ), O -methylencecalinol ( 10 ), encecalin ( 11 ), and encecalinol ( 12 ) bound to calmodulin (CaM) with higher affinity than chlorpromazine, a well-known CaM inhibitor. Molecular dynamics studies revealed that the complexes of these compounds with CaM remained stable during the simulation. Altogether these results revealed the therapeutic and research tool potential of compounds 8 , 10 , 11 , and 12 .

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway., (© 2023. The Author(s).)

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 (IC 50 3.70 μM) with standard 5-lipoxygenase inhibitor drug zileuton (IC 50 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 (IC 50 ∼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., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

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.

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.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

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.

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- β -d-glucopyranoside-2,2-dimethyl-2 H -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 IC 50 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 IC 50 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.

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.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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), β-tocotrioenol (β-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., Competing Interests: The authors declare no conflict of interest.

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., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

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., (Georg Thieme Verlag KG Stuttgart · New York.)

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 buffer–acetone 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.

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 IC 50 values of 5.3, 19.4, and 37.6 μM, respectively.

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., (© 2016 The Society for Applied Microbiology.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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 β as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.

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.

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., (© 2014 by The Mycological Society of America.)

Objectives: To identify reversal agents for the Leishmania ABCI4 transporter that confers resistance to antimony., Methods: Selective ABCI4 inhibitors among a series of 15 flavonoid and trolox derivatives or analogues were investigated by evaluating their ability to reverse antimony resistance in Leishmania parasites overexpressing ABCI4. Among the compounds screened, N-ethyltrolox carboxamide (compound D2) produced the highest reversal activity. In order to optimize the activity of D2, we synthesized a series of 10 derivatives by condensation of various amines with trolox., Results: Analysis of antimony resistance reversal activity showed that N-propyltrolox carboxamide (compound D4) was the most potent ABCI4 inhibitor, with reversal activity being maintained in the intracellular amastigote stage. In addition, trolox derivatives significantly reverted the resistance to zinc protoporphyrin. The mechanism of action of these active derivatives was found to be related to significant reversion of Sb(III) and zinc protoporphyrin accumulation and to a decrease in drug efflux., Conclusions: Our findings suggest that trolox derivatives D2 and D4 could be considered to be specific reversal agents targeting the Leishmania ABCI4 transporter. The structure-activity relationship obtained in the present study highlights the importance of the size and length of the alkyl substituent linked to trolox. Furthermore, the structural data obtained provide valuable information for the further development of new, even more specific and potent Leishmania ABCI4 reversal agents.

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).

Phytochemical investigation of a dichloromethane extract from Garcinia amplexicaulis stem bark led to the isolation of four new tocotrienols (1-4); two known tocotrienols, two triterpenes, and a xanthone were also isolated. Their structures were mainly established using NMR and MS methods. The main compounds isolated, δ-amplexichromanol (1) and γ-amplexichromanol (2), were evaluated on VEGF-induced angiogenesis using a Matrigel assay. Compounds 1 and 2 inhibited in vitro angiogenesis of VEGF-induced human primary endothelial cells in the low nanomolar range. Their capacity to inhibit VEGF-induced proliferation of endothelial cells partially explained this activity, although δ-amplexichromanol (1) also prevented adhesion and migration processes.

Ustusorane D and penicisochromans B-D are natural isochromans isolated from Aspergillus ustus 094102 and Penicillium sp. PSU-F40, respectively. Herein, we report the syntheses of (-)-ustusorane D and (+)-penicisochroman B and the structures of penicisochromans C and D. The relative configuration of natural ustusorane D and the absolute configuration of natural penicisochroman B were determined. Two plausible structures for penicisochroman C were evaluated through synthesis, but their ¹H and ¹³C NMR data were not in agreement with those of the natural product. The structural revision and the determination of the absolute configuration of natural penicisochroman D were achieved. Structure-activity relationship studies of the synthetic compounds as well as a series of related isochromans indicated that the enone of the furanone moiety was essential for the cytotoxicity of these compounds toward HCT116 human colon cancer cells. Pseudodeflectusin, the related natural isochroman, suppressed cell growth and induced apoptosis in HCT116 cells.

An extract was prepared from Egyptian stabilized rice bran and standardized to contain 2% γ-oryzanol in addition to its content of other bioactives, notably tocotrienol and policosanol. The standardized extract was found to have a concentration-dependent effect on insulin release in vitro, which, however, is not mediated by γ-tocotrienol in rice bran (detected by HPLC) as could have been expected. Policosanol and γ-oryzanol have insulinotropic effects. The in vitro data of rice bran directly translate into in vivo data of rats by using a glucose tolerance test (increase in plasma insulin). Tocotrienols are well known for their apoptotic effect on tumor cells; nevertheless, an attempt was made to study glucose uptake in HEP-G2 cells, which needs to induce an insulin-resistant state by TNF-α. The Egyptian rice bran extract has an antidiabetic effect. γ-Oryzanol, which is a possible precursor of the insulinotropic compound ferulic acid, is a candidate for this effect. Therefore, it is reasonable to assume that the prevalence of diabetes or at least a prediabetic (type 2) situation can be ameliorated by the investigated rice bran extract. The potential usefulness of the extract as a nutraceutical is currently undergoing more thorough investigations., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: To study the chemical constituents of the unmatured fruits of Citrus aurantium., Method: The AcOEt fraction of the methanol extracts of the unmatured fruits of C. aurantium were subjected on column chromatographies including silica gel, RP-18 and HPLC. Compound structures isolated were determined on the basis of spectroscopic data., Result: Three compounds were isolated from the unmatured fruits of C. aurantium, which were identified as citrauranoside (1), limonexin (2) and limonin (3)., Conclusion: Compound 1 is a new chroman glycoside derivative, named as citrauranoside.

Two new phenolics, (3S,4R)-3,7,2',3'-tetrahydroxy-3,4-dihydro-9H-indeno[6,5-c]chromene (caesalpiniaphenol E, 1), and (3R,4S)-3,7-dihydroxy-3-(3'-methoxy-4'-hydroxyphenyl)-4-methoxychroman (caesalpiniaphenol F, 2), together with eleven known compounds (3-13), were isolated from the heartwood of Caesalpinia sappan. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells. Among them, compounds 10 and 13 showed strong inhibitory activities toward the LPS-induced NO production in macrophage RAW264.7 cells, with IC(50) values of 12.5 and 8.1 μm, respectively. In addition, compounds 10 and 13 inhibited the inductions of iNOS mRNA in dose-dependent manners, indicating that these compounds attenuated the synthesis of these transcripts at the transcriptional level., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inhibited 14-3-3 protein-protein interactions (PPIs) with IC(50) values of 9.2 and 10.0 μM as determined by an ELISA assay, and 2.0 and 2.5 μM in an FP assay, respectively. These compounds represent the first example of natural small-molecule 14-3-3 inhibitors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Two new isochromans, panowamycins A and B, were purified by solvent extraction, silica gel and octadecylsilyl silica gel (ODS) column chromatography followed by preparative HPLC, from a culture broth of Streptomyces sp. K07-0010, together with the known compounds NFAT-133, conglobatin, piericidin C series and dinactin. Structures of panowamycins were elucidated as new analogs of NFAT-133 by spectroscopic studies including various NMR experiments. Panowamycins A and B showed moderate antitrypanosomal activity, with IC(50) values of 0.40 and 3.30 μg ml(-1), respectively.

We have previously demonstrated antileishmanial activity on Leishmania amazonensis of the natural (1-2), synthetic (7) and derivatives of coumarin (-) mammea A/BB (3-6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antileishmanial with LD₅₀ of 0.9 μM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z)-6-acetyl- 3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one and 6-acetyl-2α,5- dihydroxy-2-(2-hydroxypropyl)- 3α,8-dimethylchroman, respectively.

Six meroterpenoids (compounds 1-6) of chromene class, including three known compounds (1-3), were isolated from Sargassum siliquastrum. The structure of these compounds was established by extensive 2D-NMR experiments such as (1)H gradient double quantum filtered correlation spectroscopy (gDQCOSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), gradient heteronuclear multiple quantum coherence (gHMQC), and gradient heteronuclear multiple bond correlation (gHMBC), and by comparison with published spectral data. The antioxidant activity of these compounds was evaluated by various antioxidant tests, such as scavenging effects on generation of intracellular reactive oxygen species (ROS), increments of intracellular glutathione (GSH) level, and inhibitory effects on lipid peroxidation in human fibrosarcoma HT 1080 cells. Compounds (1-6) significantly decreased generation of intracellular ROS and inhibited lipid peroxidation while they increased levels of intracellular GSH at a concentration of 5 µg/ml.

Content: Vascular smooth muscle cells (VSMCs) play a major role in the pathogenesis of atherosclerosis and restenosis, and thus the excessive proliferation of VSMCs contributes to neointimal thickening during atherosclerosis and restenosis. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of the alpha-tocopherols; it acts as a potent anti-inflammatory and free-radical scavenger., Objective: The present study was designed to examine the inhibitory mechanisms of PMC in VSMC proliferation., Materials and Methods: VSMC proliferation and cytotoxicity were measured by MTT and LDH assays, respectively. The cell cycle and translocation of PKC-alpha in VSMCs were used by flow cytometry and confocal microscope, respectively. To detect PKC-alpha translocation and activation in VSMCs, immunoblotting was performed in the present study., Results: In this study, we demonstrate an anti-proliferative effect of PMC in VSMCs. Concentration-dependent inhibition of serum-induced VSMC proliferation was observed in PMC (20 and 50 muM)-treated cells. PMC pretreatment also arrested VSMC cell cycle progression at the G2/M phase. Furthermore, PMC exhibited obvious inhibitory effects on phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC)-alpha translocation and phospho-(Ser/Thr) substrate phosphorylation., Discussion and Conclusion: The inhibitory mechanisms of PMC on VSMC proliferation is mediated, at least in part, by inhibition of PKC-alpha translocation and causes cell cycle arrest in the G2/M phase. PMC treatment may represent a novel approach for lowering the risk of or improving function in abnormal VSMC proliferation-related vascular diseases.

Four new chromane derivatives, anthopogochromane (1), anthopogochromene A (2), anthopogochromene B (3), and anthopogochromene C (4), and two known compounds, daurichromenic acid (5) and ilicicolinic acid B (6), have been isolated from the Chinese medicinal plant Rhododendron anthopogonoides. The S absolute configuration of the stereogenic carbons in the chromane and chromene rings of 1-4 was determined from their circular dichroism spectra. Compounds 1 and 2 inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.

The resolution of the natural racemic chromane 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2H-1-benzopyran-6-carboxylic acid (1) isolated from the leaves of Peperomia obtusifolia has been accomplished using stereoselective HPLC. The absolute configuration of the resolved enantiomers was determined by the analysis of optical rotations and CD spectra. The finding of a racemic mixture instead of an enantiomerically pure metabolite raises questions about the final steps in the biosynthesis of this class of natural products, suggesting that the intramolecular chromane ring formation step may not be enzymatically controlled at all in P. obtusifolia., (2008 Wiley-Liss, Inc.)

Eight drimane sesquiterpenes (1-8), six isochromane derivatives (9-14), and three known compounds, daldinin B (15), 9alpha-hydroxy-6beta-[(2E,4E,6E)-octa-2,4,6-trienoyloxy]-5alpha-drim-7-en-11,12-olide (16), and pergillin (17), were isolated from the EtOAc extract of the marine-derived fungus Aspergillus ustus 094102. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxic effects on A549 and HL-60 cell lines were evaluated by SRB and MTT methods. Ustusorane E (13) showed significant cytotoxicity against HL-60 cells with an IC50 value of 0.13 microM. Ustusolates C (6) and E (8) exhibited moderate cytotoxicity against A549 and HL-60 cells with IC50 values of 10.5 and 9.0 microM, respectively, and ustusolate A (4) showed weak cytotoxicity against HL-60 and A549 cells with IC50 values of 20.6 and 30.0 microM, respectively.

Two hydroxyethylamine chroman derivatives, ammonificins A (1) and B (2), were isolated from the marine hydrothermal vent bacterium Thermovibrio ammonificans. The molecular structures of these compounds were determined using a combination of NMR, mass spectrometry, and CD analyses. Biological activities were determined using an antimicrobial assay and the patented ApopScreen cell-based screen for apoptosis induction and potential anticancer activity. To our knowledge, this is the first report of secondary metabolites from the marine hydrothermal vent bacterium T. ammonificans.

The trypanocidal activity of crude extracts and fractions from the leaves and stems of Peperomia obtusifolia (Piperaceae) was evaluated in vitro against the epimastigote forms of Trypanosoma cruzi. Bioactivity-guided fractionation of the most active extracts afforded seven known compounds, including three chromanes, two furofuran lignans and two flavone C-diglycosides. The most active compounds were the chromanes peperobtusin A and 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid, with IC (50) values of 3.1 microM (almost three times more active than the positive control benznidazole, IC (50) 10.4 microM) and 27.0 microM, respectively. Cytotoxicity assays using peritoneal murine macrophages indicated that the chromanes were not toxic at the level of the IC (50) for trypanocidal activity. This is the first report on the trypanocidal activity besides unspecific cytotoxicity of chromanes from Peperomia species. Additionally it represents the first time isolation of 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid from P. obtusifolia., (Copyright Georg Thieme Verlag KG Stuttgart. New York.)

2,5,7,8-Tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC), the water-soluble metabolite of alpha-tocopherol (alpha-TOH) with a shortened side chain but an intact hydroxychroman structure, has been identified in human urine and are thought to be produced in significant amount at excess intake of alpha-TOH. In previous studies, CEHCs in biological specimens were measured by HPLC, GC-MS or LC-MS, preceded by a hydrolysis procedure using either enzyme or methanolic HCl. In an attempt to analyze alpha-CEHC in rat urine accordingly, we observed that enzyme hydrolysis was relatively inefficient in releasing alpha-CEHC compared to high concentrations of HCl. The HCl releasable alpha-CEHC conjugate was isolated and chemically identified as 6-O-sulfated alpha-CEHC (alpha-CEHC sulfate). Using the synthetic alpha-CEHC sulfate standard, it was found that sulfatase could not hydrolyze to a significant extent. On the other hand, pretreatment with HCl at 60 degrees C in the presence of ascorbate, followed by a one-step ether extraction, not only hydrolyzed the sulfate conjugate completely but also extracted alpha-CEHC with high recovery. The inclusion of ascorbate minimized the conversion of alpha-CEHC to alpha-tocopheronolactone in the HCl pretreatment. A complete procedure for the quantitative analysis of alpha-CEHC including HCl hydrolysis, ether extraction and reverse phase isocratic HPLC-ECD was thus established. In conclusion, alpha-CEHC sulfate was isolated and identified as the HCl-releasable conjugate of alpha-CEHC in rat urine. A rapid and sensitive method with high reproducibility for the determination of free, conjugated and total alpha-CEHC is then established.

3'-Deoxy-4-O-methylepisappanol, a new 3-benzylchroman derivative, was isolated from Sappan Lignum, together with thirteen known chemical compounds identified as protosappanin A, sappanchalcone, sappanone B, palmitic acid, (+)-(8S,8'S)-bisdihydrosiringenin, brazilein, 3-deoxysappanchalcone, (+)-lyoniresinol, 3-deoxysappanone B, protosappanin B, isoprotosappanin B, 3'-O-methylbrazilin and brazilin, respectively. Among these known compounds, this is the first time that (+)-(8S,8'S)-bisdihydrosiringenin was obtained from the family Caesalpiniaceae.

Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure.

In recently, there has been a great interest in natural antioxidants as bioactive components of food, nutraceuticals or potential drugs against several diseases. In our study, 88 extracts from various parts of plants from European Asteraceae and Cichoriaceae were assayed for radical scavenging activity by means of DPPH (1,1-diphenyl-2-picryl hydrazyl radical) test using the SIA (Sequential injection analysis) method developed for this purpose in our laboratory. DPPH radical scavenging activity of all tested plant extracts was evaluated according to the IC(50) parameter. 29 extracts exhibited IC(50) value lower than 0.1 mg/mL. The leaves of Leuzea carthamoides (IC(50) = 0.046 mg/mL) were chosen as the most promising sample for a subsequent phytochemical study, which resulted in isolation of seven natural compounds, namely, 4',5,7-trihydroxy-6-methoxyflavone (hispidulin) (1), 5, 7, 3', 4'- tetrahydroxyflavanone (eriodictyol) (2), 3',4',5,7-pentahydroxy-6-methoxyflavonol (patuletin) (3), eriodictyol-7-beta-glucopyranoside (4), 6-hydroxykaempferol-7-O-(6''-O-acetyl-beta-D-glucopyranoside) (5), 4-hydroxybenzoic acid (6) and 3,4-dihydroxybenzoic acid (protocatechuic acid) (7). Antioxidant activity of the isolated compounds was evaluated by DPPH test and ferric reducing antioxidant power (FRAP) test and compared with trolox and quercetin. Both tests evaluated the flavonoid (5) as the most active antioxidant. This result was confirmed by comparison with known data concerning the structure/activity relationships of flavonoids.

Two prenylated flavanones have been isolated from the hexane extract of Phyllanthus niruri plant. The structure of these flavanones were established as 8-(3-Methyl-but-2-enyl)-2-phenyl chroman-4-one (1) and 2-(4-hydroxyphenyl)-8-(3-methyl-but-2-enyl)-chroman-4-one (2) on the basis of spectral analysis. These were evaluated for nematicidal activity against root-knot, Meloidogyne incognita, and reniform, Rotylenchulus reniformis, nematodes. Compound 2 exhibited nematicidal activity at par with the standard carbofuran (LC50 3.3 and 3.1ppm, respectively) when tested against reniform nematode. The LC50 value against root-knot nematode was found to be 14.5ppm. Compound 1 however, showed moderate activity against both the test nematodes.

Two new chromane type meroterpenoids were isolated from the methanolic extract of the brown alga, Sargassum micracanthum. Their structures were elucidated based on spectroscopic analysis and chemical conversion. The absolute stereochemistry of the methyl group at C-8' in 1 and related compounds were determined by modified Mosher's method.

2R-gamma-Tocotrienol (gamma-T3) is currently receiving attention because it has beneficial effects not observed with alpha-tocopherol. To achieve the effective delivery of gamma-T3, we synthesized three kinds of ester derivatives of gamma-T3 and evaluated their use as hydrophilic prodrugs for gamma-T3 in vitro and in vivo. 2R-gamma-Tocotrienyl N,N-dimethylamino-acetate hydrochloride (compound 3) was a solid compound, with high solubility and stability in water, and was converted to gamma-T3 by esterases in rat and human liver. Intravenous administration of 3 in rats led to a rapid increase in the plasma, liver, heart, and kidney levels of gamma-T3. The bioavailability (plasma level) after intravenous administration was 82.5 +/- 13.4% and 100 +/- 11.3% for 3 and gamma-T3 in surfactant, respectively, and the availability in liver was 213 +/- 47.6% and 100 +/- 4.8% for 3 and gamma-T3 in surfactant, respectively. Furthermore, the systemic availability of 2,7,8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman (S-gamma-CEHC), a metabolite of gamma-T3, was 78.6% for compound 3, 47.1% for gamma-T3 in surfactant, and 100% for racemic gamma-CEHC. Based on these results, we identified compound 3 as the most promising water-soluble prodrug of gamma-T3 and two-step prodrug of S-gamma-CEHC.

Two new compounds, descurainin A (1) and descurainoside B (2), were isolated from the seeds of Descurainia sophia (L.) Webb ex Prantl. Their structures were elucidated by spectroscopic methods (MS, 1H, 13C and 2D NMR).

Five clerodane diterpenoids have been isolated from the aerial parts of Pulicaria wightiana along with 3'5,6-trihydroxy-3,4',7-trimethoxyflavone and 2-methyl-5-hydroxy-chroman-4-one. The structures and stereochemistry of the compounds were established from spectral (mainly 1D and 2D NMR) studies. The last two compounds were not reported earlier from this plant. The antibacterial activity of the diterpenoids were studied.

Aim: To study the chemical constituents of Rhododendron ovatum Planch., Methods: The chemical constituents were isolated and purified by silica gel column chromatography and identified on the basis of their physiochemical and spectral data., Results: Seven compounds were isolated and identified. Their structures were established as 3,5,7-trihydroxylchromone 3-O-beta-D-xylopyranoside (I), taraxerol (II), beta-sitosterol (III), betulinic acid (IV), quercetin (V), quercetin-3-O-alpha-L-rhamnopyranoside (VI), and D-glucose (VII)., Conclusion: Compound I is a new compound. Compounds II-VII were isolated from this plant for the first time.