Copper-Catalyzed P-H Bond Functionalization to Construct Biaryl Phosphafluorene Oxides.

In this study, in the presence of a certain amount of cuprous chloride catalyst and the synergistic action of ligand and base, the P-H bond activation of secondary biarylphosphine oxides and the attack on the ß-site of orthoaryl groups were investigated. Phosphafluorene oxide was synthesized by C-H bond activation and an intramolecular dehydrogenation coupling reaction to construct a C-P bond. Subsequently, we conducted a control experiment and made reasonable speculations about its mechanism. In addition, the use of phosphafluorene as a ligand in some synthetic catalytic reactions has shown excellent results, demonstrating its excellent catalytic properties.

Vibrational Characterization and Molecular Electronic Investigations of 2-acetyl-5-methylfuran using FT-IR, FT-Raman, UV-VIS, NMR, and DFT Methods.

Spectroscopic (FT-IR, FT-Raman, UV-vis, and NMR) techniques have been extensively used for structural elucidation of compounds along with the study of geometrical and vibrational properties. Herein, 2-acetyl-5-methylfuran, a derivative of furan, was experimentally characterized and analyzed in details using FT-IR, FT-Raman, UV-vis, and 1H NMR spectroscopic techniques conducted in different solvents. The experimentally analyzed spectral results were carefully compared with theoretical values obtained using density functional theory (DFT) calculations at the B3LYP/6-311 + + G (d, p) method to support, validate, and provide more insights on the structural characterizations of the titled compound. The correlated experimental and theoretical structural vibrational assignments along with their potential energy distributions (PEDs) and all the spectroscopic spectral investigations of the titled structure were observed to be in good agreements with calculated results.

Anti-inflammatory diterpenoids from the root bark of Acanthopanax gracilistylus.

Five new ent-pimarane (1-3, 7, and 8) and three new ent-kaurane diterpenoids (4-6) and a new oleanane triterpene acid (9), together with 22 known compounds, were isolated from the root bark of the medicinal herb Acanthopanax gracilistylus. The structures of 1-9 were established based on the interpretation of high-resolution MS and 1D- and 2D-NMR data. The absolute configurations of 7 and 11 were determined by single-crystal X-ray diffraction and electronic circular dichroism analysis. Compounds 7 and 8 represent rare naturally occurring structures based on the devinyl ent-pimarane skeleton. Compounds 3, 10, 14, 16, and 17 exhibited potent inhibitory effects on the release of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) in lipopolysaccharide-stimulated peripheral blood mononuclear cells.

Inflammatory Studies of Dehydroandrographolide: Isolation, Spectroscopy, Biological Activity, and Theoretical Modeling.

Dehydroandrographolide (DA) was isolated and experimentally characterized utilizing FT-IR, UV-Vis, and NMR spectroscopy techniques along with detailed theoretical modelled at the DFT/B3LYP-D3BJ/6-311 + + G(d,p) level of theory. Substantially, molecular electronic property investigations in the gaseous phase alongside five different solvents (ethanol, methanol, water, acetonitrile and DMSO) were comprehensively reported and compared with the experimental results. The globally harmonized scale (GHS), which is used to identify and label chemicals, was also utilized to demonstrate that the lead compound predicted an LD50 of 1190 mg/kg. This finding implies that consumers can safely consume the lead molecule. Notable impacts on hepatotoxicity, cytotoxicity, mutagenicity, and carcinogenicity were likewise found to be minimal to nonexistent for the compound. Additionally, in order to account for the biological performance of the studied compound, in-silico molecular docking simulation analysis was examined against different anti-inflammatory target of enzymes (3PGH, 4COX, and 6COX). From the examination, it can be inferred that DA@3PGH, DA@4COX, and DA@6COX, respectively, showed significant negative binding affinities of -7.2 kcal/mol, -8.0 kcal/mol, and - 6.9 kcal/mol. Thus, the high mean binding affinity in contrast to conventional drugs further reinforces these results as an anti-inflammatory agent.

Macromolecular and small-molecule modulation of intracellular Aß42 aggregation and associated toxicity.

Aß (amyloid ß-peptide) has a central role in AD (Alzheimer's disease) where neuronal toxicity is linked to its extracellular and intracellular accumulation as oligomeric species. Searching for molecules that attenuate Aß aggregation could uncover novel therapies for AD, but most studies in mammalian cells have inferred aggregation indirectly by assessing levels of secreted Aß peptide. In the present study we establish a mammalian cell system for the direct visualization of Aß formation by expression of an Aß(42)-EGFP (enhanced green fluorescent protein) fusion protein in the human embryonic kidney cell line T-REx293, and use this to identify both macromolecules and small molecules that reduce aggregation and associated cell toxicity. Thus a molecular shield protein AavLEA1 [Aphelenchus avenae LEA (late embryogenesis abundant) protein 1], which limits aggregation of proteins with expanded poly(Q) repeats, is also effective against Aß(42)-EGFP when co-expressed in T-REx293 cells. A screen of polysaccharide and small organic molecules from medicinal plants and fungi reveals one candidate in each category, PS5 (polysaccharide 5) and ganoderic acid DM respectively, with activity against Aß. Both PS5 and ganoderic acid DM probably promote Aß aggregate clearance indirectly through the proteasome. The model is therefore of value to study the effects of intracellular Aß on cell physiology and to identify reagents that counteract those effects.

Diverse meroterpenoids with α-glucosidase inhibitory activity from Ganoderma cochlear.

Three new meroterpenoids, cochlearins J-L (1-3) and three known meroterpenoids (4-6) were isolated from the fruiting bodies of Ganoderma cochlear. NMR (1H and 13C NMR, 1H - 1H COSY, HSQC, HMBC and ROESY), and HRESIMS were employed for the structure elucidation of new compounds. The stereostructures of 1-3 were confirmed by calculated ECD and optical rotation methods. Furthermore, compounds (+)-1, (-)-1, (+)-2, (-)-2, (+)-3, (-)-3, and 4-6 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds (+)-1, (-)-1 and (+)-2 exhibited stronger inhibition against α-glucosidase with IC50 values of 24.18 ± 1.98, 26.49 ± 3.20 and 29.68 ± 2.73 µM, respectively, compared to the positive control ursolic acid (49.65 ± 2.21 µM). The molecular docking experiments reveal that (+)-2 and (-)-2 had different binding mode with α-glucosidase, leading to their different inhibition.

Asperidulins A and B, two new prenylxanthone derivatives from an apple-derived fungus Aspergillus nidulans KIB-HACM-01.

Two new prenylxanthone derivatives, asperidulins A (1) and B (2), along with a known emodin analogue (3) were isolated from an apple-derived fungus Aspergillus nidulans KIB-HACM-01. Their structures were elucidated by interpretation of HRMS, NMR, and comparisons of specific optical rotation. Asperidulin B (2) exhibited a moderate cytotoxicity against A549 and BEAS-2B with an IC50 values of 13.62 ± 0.41 and 11.27 ± 0.52 µM, and methyl-averantin (3) showed moderate cytotoxicities against all six tested cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, SW480, BEAS-2B) with IC50 values ranging from 8.93 ± 0.56 to 35.27 ± 0.25 µM.

Investigation on the molecular, electronic and spectroscopic properties of rosmarinic acid: an intuition from an experimental and computational perspective.

Various drugs such as corticosteroids, salbutamol, and ß2 agonist are available for the treatment of asthma an inflammatory disease and its symptoms, although the ingredient and the mode of action of these drugs are not clearly elucidated. Hence this research aimed at carrying out improved scientific research with respect to the use of natural product rosmarinic acid which poses minima, side effects. Herein, we first carried out extraction, isolation, and spectroscopic (FT-IR, 1H-NMR and 13C-NMR) investigation, followed by molecular modeling analysis on the naturally occurring rosmarinic acid extracted from Rosmarinus officinalis. A detailed comparison of the experimental and theoretical vibrational analysis has been carried out using five DFT functionals: BHANDH, HSEH1PBE, M06-2X, MPW3PBE and THCTHHYB with the basis set 6-311++G (d, p) to investigate into the structural, reactivity, and stability of the isolated compound. Frontier molecular orbital analysis and appropriate quantum descriptors were calculated. Results showed that the compound was more stable at M06-2X and more reactive at HSEH1PBE with an energy gap of 6.43441 eV and 3.8047 eV, respectively, which was later affirmed by the global quantum reactivity parameters. From natural bond orbital analysis, π* →π* is the major contributor to electron transition with the summation perturbation energy of 889.57 kcal/mol, while π →π* had the perturbation energy totaling of 145.3 kcal/mol. Geometry analysis shows BHANDH to have lower bond length values and lesser deviation from 120° in carbon-carbon angle. The potency of the title molecule as an asthma drug was tested via a molecular docking approach and the binding score of -8.2 kcal/mol was observed against -7.0 of salbutamol standard drug, suggesting romarinic acid as a potential natural organic treatment for asthma.Communicated by Ramaswamy H. Sarma.

Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38-MAPK/FoxO3 pathway in cancer cachexia.

BACKGROUND: Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone-induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms. METHODS: C26 tumour-bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF-α-induced C2C12 myotubes or ad-mRFP-GFP-LC3B-transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy-lysosome system. The possible direct targets of CYA were searched using the biotin-streptavidin pull-down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay. RESULTS: The administration of CYA prevented body weight loss and muscle wasting in C26 tumour-bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P < 0.05. The values of gastrocnemius muscle weight/body weight of mice treated with 15 or 30 mg/kg CYA (0.53 ± 0.02% and 0.54 ± 0.01%, respectively) were both significantly higher than that of the C26 model group (0.45 ± 0.01%) with P < 0.01. CYA decreased both UPS-mediated protein degradation and autophagy in muscle tissues of C26 tumour-bearing mice as well as in C2C12 myotubes treated with TNF-α. The thousand-and-one amino acid kinase 1 (TAOK1) was found to be the direct binding target of CYA. CYA inhibited the activation of TAOK1 and its downstream p38-MAPK pathway thus decreased the level and nuclear location of FoxO3. siRNA knockdown of TAOK1 or regulation of the p38-MAPK pathway using activator or inhibitor could affect the ameliorating effects of CYA on myotube atrophy. CONCLUSIONS: CYA ameliorates cancer cachexia muscle atrophy by decreasing both UPS degradation and autophagy. The ameliorating effects of CYA on muscle atrophy might be based on its binding with TAOK1 and inhibiting the TAOK1/p38-MAPK/FoxO3 pathway.

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research. Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed. Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol. Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Carnosol attenuated atrophy of C2C12 myotubes induced by tumour-derived exosomal miR-183-5p through inhibiting Smad3 pathway activation and keeping mitochondrial respiration.

Cancer-derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour-bearing mice in our previous study, alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR-183-5p was found to be rich in C26 cells and C26 exosomes, and miR-183-5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 µM could dose-dependently ameliorate the myotube atrophy induced by miR-183-5p. Four and a half LIM domain protein 1 (FHL1) was shown to be the direct target of miR-183-5p. Increase in myostatin, p-Smad3, MuRF-1, Atrogin-1, HIF-1α and p-STAT3 and decrease in mitochondrial respiration were also induced by miR-183-5p mimic in C2C12 myotubes. Carnosol could not affect the decrease in FHL-1 and the activation of STAT3 pathway but could significantly alleviate the increase in myostatin, p-Smad3, MuRF-1, Atrogin-1 and the decrease in mitochondrial respiration induced by miR-183-5p. The protective effects of carnosol on myotubes against atrophy of C2C12 myotubes induced by miR-183-5p, based on both its inhibiting effects on MuRF-1 and Atrogin-1-mediated protein degradation and its ability of keeping the mitochondrial respiration, might contribute to its ameliorating effects on cancer cachexia.

Fragmentation pathways of oxygenated tetracyclic triterpenoids and their application in the qualitative analysis of Ganoderma lucidum by multistage tandem mass spectrometry.

The fragmentation pathways of oxygenated tetracyclic triterpenoids from Ganoderma lucidum were systematically studied based on interpreting the mass spectra of 44 known triterpenoids using a combination of multistage tandem mass spectrometry (MS(n)) experiments and high-resolution mass spectrometry (HRMS) analysis. In negative ion mode, the fragmentation pathways of triterpenoid acids are rather characteristic. After the prominent loss of H(2) O or CO(2), cleavages take place on the A, B, C and D rings. Interestingly, the cleavage mode is highly dependent on the positions of the carbonyl groups and hydroxyl groups in the tetracyclic skeleton. Characteristic cleavage of ring A occurs in 7-oxo-11-H or 7-oxo-11-hydroxy derivatives; characteristic cleavage of ring B occurs in the 7-oxo-11-hydroxy derivatives; characteristic cleavage of ring C occurs in the 7-hydroxy-15-oxo derivatives; while the cleavage of ring D can be observed in the majority of the compounds investigated. The odd-electron species, which disobey the 'even-electron rule', are also observed and discussed in this paper. These phenomena provide an easy way to determine the tetracyclic skeleton and distinguish the isomers of the triterpenoids from each other. What is more, the fragmentation pathways of triterpenoid alcohols were also investigated in positive ion mode. The accurate masses of the product ions were determined using quadrupole orthogonal time-of-flight (QTOF) instruments. Finally, the fragmentation rules were applied to identify the components of G. lucidum. As a result, 73 triterpenoids including 11 new ones were identified. The triterpenoids were classified into six subclasses according to their different fragmentation behaviors. The application of tandem mass spectrometry was further explored.

Pharmacophore-based discovery of FXR-agonists. Part II: identification of bioactive triterpenes from Ganoderma lucidum.

The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its ligand-binding domain renders FXR an attractive target for in silico approaches. Integrated to natural product research these computational tools assist to find novel bioactive compounds showing beneficial effects in prevention and treatment of, for example, the metabolic syndrome, dyslipidemia, atherosclerosis, and type 2 diabetes. Virtual screening experiments of our in-house Chinese Herbal Medicine database with structure-based pharmacophore models, previously generated and validated, revealed mainly lanostane-type triterpenes of the TCM fungus Ganoderma lucidum Karst. as putative FXR ligands. To verify the prediction of the in silico approach, two Ganoderma fruit body extracts and compounds isolated thereof were pharmacologically investigated. Pronounced FXR-inducing effects were observed for the extracts at a concentration of 100 µg/mL. Intriguingly, five lanostanes out of 25 secondary metabolites from G. lucidum, that is, ergosterol peroxide (2), lucidumol A (11), ganoderic acid TR (12), ganodermanontriol (13), and ganoderiol F (14), dose-dependently induced FXR in the low micromolar range in a reporter gene assay. To rationalize the binding interactions, additional pharmacophore profiling and molecular docking studies were performed, which allowed establishing a first structure-activity relationship of the investigated triterpenes.

Acetylated anthraquinone glycosides from Cassia obtusifolia.

Three new acetylated anthraquinone glycosides (1-3) were isolated from the seed of Cassia obtusifolia, together with one parent anthraquinone glycoside (1a). Their structures were determined on the basis of spectroscopic methods and physicochemical properties as obtusifoline-2-O-ß-d-2, 6-di-O-acetylglucopyranoside (1), obtusifoline-2-O-ß-d-glucopyranoside (1a), obtusifoline-2-O-ß-d-3, 6-di-O-acetylglucopyranoside (2), and obtusifoline-2-O-ß-d-4, 6-di-O-acetylglucopyranoside (3).

Anticorrosion and dispersive adsorption studies of natural andrographolide on carbon steel in acid-chloride environments.

Andrographolide, a bioactive naturally occurring labdane diterpenoid with outstanding antioxidant effects in medicine, has been isolated and purified from Andrographis paniculata, and applied in acid-chloride environments for the corrosion protection of carbon steel. Upon isolation, the phytochemical was identified by NMR and FTIR, while its corrosion inhibition evaluation was achieved by combined electrochemical and gravimetric experiments. The adsorption of andrographolide on carbon steel was examined by SEM, FTIR, and 3D surface measurement, and computational studies were used to describe the adsorption characteristics and properties. The experimental measurements revealed that andrographolide is an effective mixed-type corrosion inhibitor whose efficiency was dependent on both its concentration and the temperature of the environment, with maximum inhibition efficiency of 92.4% recorded for 2.0 g/L andrographolide after 48 h at 318 K. The adsorption of andrographolide and its anticorrosion capacity on carbon steel surface was confirmed by the employed surface analytical techniques, while molecular electrostatic potential, conceptual density functional theory, and molecular dynamics simulation predicted the quantum chemical details and binding properties of the phytochemical on Fe (110) surface at different temperatures.

A new phenanthropyran and a new biphenanthrene from the rhizomes of Dioscorea septemloba and their antioxidant activities.

A new phenanthropyran, dioscorone B (1), and a new phenanthrene (2), together with seven known compounds (3-9), were isolated from the 75% ethanol extract of Dioscorea septemloba rhizomes. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, and UV spectra. Compounds 1-5 were first isolated from genus Dioscorea. The proton and carbon chemical shifts of compounds 1-9 were unambiguously assigned based on the 1D-NMR and 2D-NMR data. Compounds 1-5 and 8-9 were first tested for their antioxidant activities. Compounds 1 and 2 showed excellent activities with IC50 values of 0.07 ± 0.10 µM and 0.13 ± 0.09 µM, respectively.

Three new biflavonoids from the branches and leaves of Cephalotaxus oliveri and their antioxidant activity.

Three new biflavonoids, named oliveriflavones A-C (1-3), together with two known flavonoids (quercetin (4) and rutin (5)), were isolated from the endangered plant Cephalotaxus oliveri. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, UV, and CD spectra. Compounds 1-5 were first isolated from the genus Cephalotaxus. All the compounds were tested for their antioxidant activity. Compounds 4 and 5 showed excellent activity with IC50 values of 0.03 ± 0.06 µM and 0.02 ± 0.10 µM, respectively.

Detailed characterization of Phellodendron chinense Schneid and its application in the corrosion inhibition of carbon steel in acidic media.

We present a combined experimental and theoretical study of the effective corrosion protection of carbon steel in 1 M HCl solution by Phellodendron chinense Schneid (PCS) bark extract. Fourier-transform infrared spectroscopy (FTIR) and liquid chromatography tandem multi-stage mass spectrometry (LC-MSn) were employed for the extract characterization. The properties of PCS as a corrosion inhibitor were evaluated by electrochemical and gravimetric experiments. Quantum chemical calculation was used to describe the electronic and adsorption properties of the identified and characterized compounds found in the extract while molecular dynamics simulation was employed to predict the equilibrium configurations and binding energies of the compounds on the steel surface. The electrochemical results revealed that PCS acted as a mixed-type corrosion inhibitor whose efficiency increased with the extract concentration but slightly decreased with increasing temperature. Quantum chemical parameters, such as the energy difference (ΔE) and the number of transferred electrons (ΔN), were used to predict the contribution of each characterized compound to the inhibition process while molecular dynamics simulation predicted parallel orientations for the configuration of the compounds and high binding energies on the metal substrate.

ß-L-Arabinofuranosylation Conducted by 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl Trichloroacetimidate.

We describe a ß-L-arabinofuranosylation method by employing the 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl trichloroacetimidate 10 as a donor. This approach allows a wide range of acceptor substrates, especially amino acid acceptors, to be used. Stereoselective synthesis of ß-(1,4)-L-arabinofuranosyl-(2S, 4R)-4-hydroxy-L-proline (ß-L-Araf-L-Hyp4) and its dimer is achieved readily by this method. Both the stereoselectivities and yields of the reactions are excellent. To demonstrate the utility of this methodology, the preparation of a trisaccharide in a one-pot manner was carried out.

Three new alkaloids isolated from the stem tuber of Pinellia pedatisecta.

The present study was designed to determine the chemical constituents of the stem tuber of Pinellia pedatisecta. The chemical constituents were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Three new alkaloids (compounds 1, 2, and 3) were obtained and identified as 9-((5-methoxypyridin-2-yl)methyl)-9H-purin-6-amine (1), 4-(2-(2, 5-dioxopyrrolidin-1-yl)ethyl)phenyl acetate (2), and N-(9-((5-methoxypyridin-2-yl)methyl)-9H-purin-6-yl)acetamide (3). These compounds were evaluated for their cytotoxicity against human cervical cancer HeLa cells. Compounds 1 and 3 significantly inhibited the proliferation of HeLa cells with IC50 values being 3.02 ± 0.54 and 7.16 ± 0.62 µmol·L-1, respectively.