Citreobenzofuran D-F and Phomenone A-B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494.

Five new sesquiterpenoids, citreobenzofuran D-F (1-3) and phomenone A-B (4-5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E-F (2-3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 µM.

Naphthalenones and Naphthols Isolated from the Saussurea laniceps Endophytic Fungus Didymella glomerata X223.

One new naphthalenone, didymelol A, and three new naphthols, didymelol B-D, together with three known naphthalenones, (3S,4R)-3,4,6-trihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4,6-dihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4-hydroxy-3,4-dihydronaphthalen-1(2H)-one, were isolated from the Saussurea laniceps endophytic fungus Didymella glomerata X223. The structures of the isolates were elucidated based on extensive spectroscopic data analysis. The absolute configuration of didymelol A was established through single-crystal X-ray diffraction data and didymelols B-D were identified through comparisons of experimental and calculated ECD spectra. All compounds were evaluated for cytotoxic activity against human non-small cell lung cancer A549 cells and human breast carcinoma MDA-MB-435 cells.

Protective effect of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl isolated from Annulohypoxylon annulatum against streptozotocin-induced damage in INS-1 cells.

We evaluated the protective effects of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl (BNT) isolated from Annulohypoxylon annulatum on pancreatic ß-cell apoptosis, using the ß-cell toxin streptozotocin (STZ). Hypoxylonol C and BNT restored the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 µM STZ resulted in an increase in apoptotic cell death, which was observed as annexin V fluorescence intensity. Apoptotic cell death was decreased by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. Similarly, STZ caused a marked increase in the expression of cleaved caspase-8, caspase-3, Bax, and poly (ADP-ribose) polymerase (PARP), as well as a decrease in the expression of B-cell lymphoma 2 (Bcl-2), which was reversed by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. These findings suggest that hypoxylonol C and BNT play an important role in protecting pancreatic ß-cells against apoptotic damage.

Mono- and Dimeric Naphthalenones from the Marine-Derived Fungus Leptosphaerulina chartarum 3608.

Five new naphthalenones, two enantiomers (−)-1 and (+)-1 leptothalenone A, (−)-4,8-dihydroxy-7-(2-hydroxy-ethyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one ((−)-2), (4S, 10R, 4’S)-leptotha-lenone B (5), (4R, 10S, 4’S)-leptothalenone B (6), and a new isocoumarine, 6-hydroxy-5,8-dimethoxy-3-methyl-1H-isochromen-1-one (4), along with two known compounds (+)-4,8-dihydroxy-7-(2-hydroxy-ethyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one ((+)-2) and (+)-10-norparvulenone (3) were isolated from the marine-derived fungus Leptosphaerulina chartarum 3608. The structures of new compounds were elucidated by HR-ESIMS, NMR, and ECD analysis. All compounds were evaluated for cytotoxicity and anti-inflammatory activity. Compound 6 showed moderate anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells, with an IC50 value of 44.5 μM.

Synthesis and evaluation of pseudopeptide chiral stationary phases for enantioselective resolution.

Poly(2-oxazoline)s are regarded as bioinspired polymers due to their structural relation to polypeptides. In this work, a new kind of poly(2-oxazoline)s containing dipeptide segments in the side chains was synthesized through a bottom-up protocol, which involves ring-opening copolymerization of 2-(N-Boc-l-2-pyrrolidinyl)-2-oxazoline (PyOXBoc) with 2-(3-butenyl)-2-oxazoline (BuOX) followed by deprotection and amide coupling with N-protected L-proline. The resulting vinyl-functionalized polymers were subsequently immobilized onto mercaptopropylated silica bead matrices by means of thio-click chemistry and their potential as the chiral stationary phase (CSP) for high-performance liquid chromatography was preliminarily evaluated with a series of structurally different racemates. The results showed that this class of pseudopeptide CSPs is particularly adapted to the enantiomeric separation of 1,1'-bi-2-naphthol and acyloin compounds (such as benzoin) under normal-phase conditions. Moreover, an increase in the length of polymer main chains is beneficial to the enhancement of both enantioselectivity and resolution ability. The chiral discrimination of analytes by the polymeric selectors stems primarily from hydrogen bonding and π-π interactions as well as steric hindrance.

Ancistectorine D, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8'- and 7,1'-linked metabolites from the Chinese liana Ancistrocladus tectorius.

From the twigs and stems of the Chinese liana Ancistrocladus tectorius (Ancistrocladaceae), two new 5,8'-coupled naphthylisoquinolines, ancistectorine D (5) and its 6-O-demethyl derivative 6, were isolated, along with two new 7,1'-linked alkaloids, 6-O-methylancistectorine B1 (7) and ancistectorine B2 (8). Two further compounds, ancistroealaine A (4) and 6-O-demethyl-8-O-methyl-7-epi-ancistrobrevine D (10), already known from related Asian and African Ancistrocladus species, were discovered for the first time in A. tectorius. The structure elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and chiroptical (circular dichroism) methods. Chemotaxonomically remarkable, 5,8'-coupled naphthylisoquinolines have as yet been found quite rarely in Asian Ancistrocladus species, where only two examples have so far been detected, while alkaloids with this coupling type represent the by far the largest group of constituents in African taxa. Ancistectorine D (5) shows promising activities against the protozoan parasites Trypanosoma cruzi and Leishmania donovani, and it was likewise found to display strong cytotoxic activities against human leukemia (CCRF-CEM) and multidrug-resistant tumor cells (CEM/ADR5000).

Cladosporinone, a new viriditoxin derivative from the hypersaline lake derived fungus Cladosporium cladosporioides.

A new cytotoxic viriditoxin derivative, cladosporinone (1), along with the known viriditoxin (2) and two viriditoxin derivatives (3 and 4) were obtained from the fungus Cladosporium cladosporioides isolated from the sediment of a hypersaline lake in Egypt. The structure of the new compound (1) was determined by 1D and 2D NMR measurements as well as by high-resolution ESIMS and electronic circular dichroism spectroscopy. All isolated compounds were studied for their cytotoxicity against the murine lymphoma cell line L5187Y and for their antibiotic activity against several pathogenic bacteria. Viriditoxin (2) was the most active compound in both bioassays. Compound 1 also exhibited strong cytotoxicity against the murine lymphoma cell line L5187Y with an IC50 value of 0.88 µm, whereas its antibiotic activity was weak.

Anti-inflammatory effect of desoxo-narchinol-A isolated from Nardostachys jatamansi against lipopolysaccharide.

We previously reported that Nardostachys jatamansi (NJ) exhibits anti-inflammatory activity against lipopolysaccharide (LPS). However, the active compound in NJ is unknown. Therefore, here, we examined the effects of desoxo-narchinol-A (DN) isolated from NJ against LPS-induced inflammation. To demonstrate the anti-inflammatory effect of DN against LPS, we used two models; murine endotoxin shock model for in vivo model, and peritoneal macrophage responses for in vitro. In endotoxin shock model, DN was administrated intraperitoneally 1h before LPS challenge, then we evaluated mice survival rates and organ damages. Pretreatment with DN (0.05mg/kg, 0.1mg/kg, or 0.5mg/kg) dramatically reduced mortality in a murine LPS-induced endotoxin shock model. Furthermore, DN inhibited tissue injury and production of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α), in the liver and lung. In in vitro macrophage model, we examined the inflammatory mediators and regulatory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB). DN inhibited the production of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and its derivative nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), IL-1ß, IL-6 and TNF-α and H3 protein acetylation in murine peritoneal macrophages. DN also inhibited p38 activation, but not extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and NF-κB. These results suggest that DN from NJ exhibits protective effects against LPS-induced endotoxin shock and inflammation through p38 deactivation.

Identfication of new naphthalenones from Juglans mandshurica and evalution of their anticancer activities.

Two new naphthalenone compounds were isolated from green walnut husks of Juglans mandshurica and their structures were identified as 4-butoxybutoxy-5,8-dihydroxy-3,4-dihydro-2H-naphthalen-1-one (1), 4-ethoxyethoxy-5,8-dihydroxy-3,4-dihydro-2H-naphthalen-1-one (2). Compounds 1 and 2 were named as Juglanstetralone A (1) and Juglanstetralone B (2). Compound 1 showed more significant anti-tumor activity than 2 against gastric cancer BGC-823 cells, wih the IC50 of 125.89 (g(mL(-1).

Coextraction of acidic, basic and amphiprotic pollutants using multiwalled carbon nanotubes/magnetite nanoparticles@polypyrrole composite.

The simultaneous extraction of acidic, basic and amphiprotic pollutants from various samples is a considerable and disputable concept in sample preparation strategies. In this study, for the first time, coextraction of acidic, basic and amphiprotic pollutants (polar and apolar) with multiwalled carbon nanotubes/Fe3O4@polypyrrole (MWCNTs/Fe3O4@PPy) composite based dispersive micro-solid phase extraction followed by high performance liquid chromatography-photo diode array detection was introduced. Firstly, the extraction efficiency of various magnetic nanosorbents including Fe3O4, MWCNTs/Fe3O4, graphene oxide/Fe3O4 (GO/Fe3O4), Fe3O4@PPy, MWCNTs/Fe3O4@PPy and GO/Fe3O4@PPy were compared. The results revealed that MWCNTs/Fe3O4@PPy nanocomposite has higher extraction efficiency for five selected model analytes (4-nitrophenol, 3-nitroaniline, 2,4-dichloroaniline, 3,4-dichloroaniline and 1-amino-2-naphthol). Box-Behnken design methodology combined with desirability function approach was applied to find out the optimal experimental conditions. The opted conditions were: pH of the sample, 8.2; sorbent amount, 12 mg; sorption time, 5.5 min; salt concentration, 14% w/w; type and volume of the eluent, 120 µL acetonitrile; elution time; 2 min. Under the optimum conditions detection limits and linear dynamic ranges were achieved in the range of 0.1-0.25 µg L(-1) and 0.5-600 µg L(-1), respectively. The percent of extraction recovery and relative standard deviations (n=5) were in the range of 45.6-82.2 and 4.0-8.5, respectively. Ultimately, the applicability of this method was successfully confirmed by analyzing rain, snow and river water samples and satisfactory results were obtained.

A new naphthalene glycoside from Chimaphila umbellata inhibits the RANKL-stimulated osteoclast differentiation.

A new naphthalene glycoside was isolated from the leaves and stems of Chimaphila umbellata Barton. Its chemical structure was elucidated to be 2,7-dimethyl-1,4-dihydroxynaphthalene-1-O-ß-D-glucopyranoside (DMDHNG), based on spectroscopic evidence. DMDHNG significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, the new glycoside inhibited the RANKL-induced mRNA expression of osteoclast-associated genes that encode TRAP, cathepsin K, and another transcription factor-nuclear factor of activated T-cells c1. We believe that the inhibitory effects of DMDHNG on the osteoclast differentiation may be exploited for a therapeutic benefit.

Divinyl sulfone cross-linked cyclodextrin-based polymeric materials: synthesis and applications as sorbents and encapsulating agents.

The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), ß-cyclodextrin (ß-CD) and/or starch generates a variety of homo- and hetero-CDPs with different degrees of crosslinking as a function of the reactants' stoichiometric ratio. The novel materials were characterized by powder X-ray diffraction, electron microscopy and for their sorption of phenol and 4-nitrophenol. They were further evaluated as sorbents with phenolic pollutants (bisphenol A and ß-naphthol) and bioactive compounds (the hormone progesterone and curcumin). Data obtained from the inclusion experiments show that the degree of cross-linking has a minor influence on the yield of inclusion complex formation and highlight the important role of the CDs, supporting a sorption process based on the formation of inclusion complexes. In general, the inclusion processes are better described by a Freundlich isotherm although an important number of them can also be fitted to the Langmuir isotherm with R2 ≥ 0.9, suggesting a sorption onto a monolayer of homogeneous sites.

Karwinaphthopyranones from the fruits of Karwinskia parvifolia and their cytotoxic activities.

The new 2-acetyl-8-methoxynaphthol (1) and five new "dimeric" napthopyranones, karwinaphthopyranones A1 and A2 (2 and 3) and karwinaphthopyranones B1-B3 (4-6), possessing a methoxy group at C-5', were isolated together with four other known compounds from the dried fruits of Karwinskia parvifolia. The structures of compounds 2-6 were determined by spectroscopic data interpretation. Cell culture assays showed that some of these compounds possess antiproliferative activities in representative human cancer cell lines, with half-maximal growth inhibitory concentrations in the micromolar range.

A new naphthol from the twigs and leaves of Pterospermum yunnanense.

A new naphthol, 7-hydroxy-6-methyl-1-naphthoic acid methyl ester (1), together with eight known compounds, 6-hydroxy-7-(hydroxymethyl)-1-isopropyl-4-methyl-naphthalene (2), α-hydroxyacetosyringone (3), hexadecyl ferulate (4), scoparone (5), (+)-syringaresinol (6), stigmast-1,5-dien-3ß-ol (7), ß-sitosterol (8) and daucosterol (9), were isolated from the twigs and leaves of Pterospermum yunnanense Hsue. Their structures were elucidated by using spectroscopic analysis. All the compounds were isolated for the first time from P. yunnanense Hsue. Compound 1 was assessed for its cytotoxicity against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that it has no activity.

Five novel naphthylisoquinoline alkaloids with growth inhibitory activities against human leukemia cells HL-60, K562 and U937 from stems and leaves of Ancistrocladus tectorius.

Two new 7,6'-coupled naphthylisoquinolines, namely ancistrotectorines A (1) and B (2), two new 5,3'-coupled naphthylisoquinolines, namely ancistrotectorines C (3) and D (4), and one new 7,8-coupled naphthylisoquinoline, namely ancistrotectorine E (5), together with 9 known naphthylisoquinoline alkaloids, hamatine (6), ancistrobertsonine B (7), ancistrocladinine (8), hamatinine (9), ancistrotanzanine A (10), ancistrotanzanine B (11), ancistrotectoriline B (12), 7-epi-ancistrobrevine D (13), and ancistrotectorine (14), were isolated from the 70% EtOH extract of Ancistrocladus tectorius. Their structures were elucidated based on the extensive analysis of spectroscopic data (1D, 2D NMR and MS). Compound 5 exhibited inhibitory activities against HL-60, K562 and U937 cell lines with IC50 values of 1.70, 4.18 and 2.56 µM respectively.

Dispersive liquid-liquid microextraction of pesticides and metabolites from soils using 1,3-dipentylimidazolium hexafluorophosphate ionic liquid as an alternative extraction solvent.

In this work, the use of the ionic liquid (IL) 1,3-dipentylimidazolium hexafluorophosphate ([PPIm][PF6]) as an alternative extractant for IL dispersive liquid-liquid microextraction (IL-DLLME) of a group of pesticides and metabolites (2-aminobenzimidazole, carbendazim/benomyl, thiabendazole, fuberidazole, carbaryl, 1-naphthol, and triazophos) from soils is described. After performing an initial ultrasound-assisted extraction (USE), the IL-DLLME procedure was applied for the extraction of these organic analytes from soil extracts. Separation and quantification was achieved by high-performance liquid chromatography (HPLC) with fluorescence detection (FD). Calibration, precision, and accuracy of the described USE-IL-DLLME-HPLC-FD method using [PPIm][PF6] as an alternative extractant was evaluated with two soils of different physicochemical properties. Accuracy percentages were in the range 93-118% with RSD values below 20%. A comparison of the performance of [PPIm][PF6] versus that of the so-common 1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIm][PF6]) was accomplished. Results indicate a comparable extraction efficiency with both ILs, being slightly higher with [HMIm][PF6] for the metabolite 2-aminobenzimidazole, and slightly higher with [PPIm][PF6] for triazophos. In all cases, LODs were in the low ng/g range (0.02-14.2 ng/g for [HMIm][PF6] and 0.02-60.5 ng/g for [PPIm][PF6]). As a result, the current work constitutes a starting point for the use of the IL [PPIm][PF6] for further analytical approaches.

Identification of natural diterpenes that inhibit bacterial wilt disease in tobacco, tomato and Arabidopsis.

The soil-borne bacterial pathogen Ralstonia solanacearum invades a broad range of plants through their roots, resulting in wilting of the plant, but no effective protection against this disease has been developed. Two bacterial wilt disease-inhibiting compounds were biochemically isolated from tobacco and identified as sclareol and cis-abienol, labdane-type diterpenes. When exogenously applied to their roots, sclareol and cis-abienol inhibited wilt disease in tobacco, tomato and Arabidopsis plants without exhibiting any antibacterial activity. Microarray analysis identified many sclareol-responsive genes in Arabidopsis roots, including genes encoding or with a role in ATP-binding cassette (ABC) transporters, and biosynthesis and signaling of defense-related molecules and mitogen-activated protein kinase (MAPK) cascade components. Inhibition of wilt disease by sclareol was attenuated in Arabidopsis mutants defective in the ABC transporter AtPDR12, the MAPK MPK3, and ethylene and abscisic acid signaling pathways, and also in transgenic tobacco plants with reduced expression of NtPDR1, a tobacco homolog of AtPDR12. These results suggest that multiple host factors are involved in the inhibition of bacterial wilt disease by sclareol-related compounds.

Purified vitexin compound 1 suppresses tumor growth and induces cell apoptosis in a mouse model of human choriocarcinoma.

OBJECTIVE: In our previous study, we had isolated a series of lignan compounds, termed vitexins, from the seed of Chinese herb Vitex negundo and found broad antitumor activities of these compounds in many cancer xenograft models and cell lines. This study was aimed to determine the antitumor effect of purified vitexin compound 1 (VB1) on choriocarcinoma in vitro and in vivo. MATERIALS AND METHODS: The severe combined immunodeficiency mouse model of choriocarcinoma was established to investigate the in vivo effect of VB1. Its effect on proliferation and apoptosis in JEG-3 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay and flow cytometry, respectively. The expression of caspase-3, Bcl-2, and some molecules involved in the mammalian target of rapamycin (mTOR) signaling was detected by Western blot. RESULTS: Vitexin compound 1 significantly inhibited the growth of choriocarcinoma in severe combined immunodeficient mice and reduced the serum ß-human chorionic gonadotropin level. Vitexin compound 1 inhibited cell proliferation, induced apoptosis, and inhibited the mTOR signaling in JEG-3 cell line. CONCLUSION: Vitexin compound 1 could inhibit choriocarcinoma via inducing cell apoptosis and suppressing the mTOR pathway.

A liquid chromatography tandem mass spectrometry method for simultaneous determination of acid/alkaline phytohormones in grapes.

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of five acid/alkaline phytohormones, i.e., indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), naphthylacetic acid (NAA), gibberellic acid (GA(3)) and isopentenyladenine (2IP), in grapes was developed. After optimization, the samples were extracted with methanol containing 1% formic acid and purified by Oasis HLB SPE cartridges. The analytes were separated on a Thermo Hypersil Gold column (100 mm×2.1 mm, 3.0 µm) with water and acetonitrile, then determined with Thermo tandem quadrupole mass spectrometer operating in negative electro-spray ionization using selected reaction monitoring (SRM) mode. The established method was further validated by determining the linearity (R² ≥ 0.9990), average recovery (82.5-105.4%), sensitivity (0.05-1.00 ng mL⁻¹), precision (RSD ≤1 3.0%) and stability (RSD ≥ 82.0%). Finally, the application of the approach proposed to thirty grape samples convinced its desirable performance for rapid analysis of multiclass phytohormones, supporting its sufficient capability for multiresidue analyses or other analytical system targeting phytohormones in agriculture field.

Simultaneous determination of eight common odors in natural water body using automatic purge and trap coupled to gas chromatography with mass spectrometry.

Production and fate of taste and odor (T&O) compounds in natural waters are a pressing environmental issue. Simultaneous determination of these complex compounds (covering a wide range of boiling points) has been difficult. A simple and sensitive method for the determination of eight malodors products of cyanobacterial blooms was developed using automatic purge and trap (P&T) coupled with gas chromatography-mass spectrometry (GC-MS). This extraction and concentration technique is solvent-free. Dimethylsulfide (DMS), dimethyltrisulfide (DMTS), 2-isopropyl-3-methoxypyrazine (IPMP), 2-isobutyl-3-methoxypyrazine (IBMP), 2-methylisoborneol (MIB), ß-cyclocitral, geosmin (GSM) and ß-ionone were separated within 15.3 min. P&T uses trap #07 and high-purity nitrogen purge gas. The calibration curves of the eight odors show good linearity in the range of 1-500 ng/L with a correlation coefficient above 0.999 (levels=8) and with residuals ranging from approximately 83% to 124%. The limits of detection (LOD) (S/N=3) are all below 1.5 ng/L that of GSM is even lower at 0.08 ng/L. The relative standard deviations (RSD) are between 3.38% and 8.59% (n=5) and recoveries of the analytes from water samples of a eutrophic lake are between 80.54% and 114.91%. This method could be widely employed for monitoring these eight odors in natural waters.