Antifouling activity of terpenoids from the corals Sinularia flexibilis and Muricella sp. against the bryozoan Bugula neritina.

Marine natural products are promising sources of green antifoulants. Here, a new compound (1) was isolated from the soft coral Sinularia flexibilis. This compound, another nine cembranoids (2-10) from S. flexibilis, and three eunicellin-type diterpenoids (11-13) from the gorgonian Muricella sp. were tested for antifouling activity against larval settlement of the bryozoan Bugula neritina. Compounds 2, 3, 4, 9, 12, and 13 exhibited significant antifouling activity, with EC50 values of 18.2, 99.7, 67.9, 35.6, 33.9, and 49.3 µM, respectively. Analysis of the structure-activity relationships suggested that the hydroxy group at C-13 in compound 4 reduced its antifouling activity.

New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai.

Ten new diarylheptanoid dimers, katsumadainols C1 - C10 (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 µM) and 117.8-348.2% (12.5 µM). Compounds 1-4 exhibited significant inhibition on GPa with IC50 values of 18.0-31.3 µM; compounds 1-5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9-18.2 µM; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 µM. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.

Tsaokopyranols A-M, 2,6-epoxydiarylheptanoids from Amomum tsao-ko and their α-glucosidase inhibitory activity.

The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α-glucosidase inhibitory activity with an IC50 value of 38.6 µg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A-M (1-13), and four known ones (14-17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4-6, 8-11) and one known (16) compounds showed obvious α-glucosidase inhibitory activity with IC50 values ranging from 59.4 to 116.5 µM, higher than acarbose (IC50: 219.0 µM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α-glucosidase with Ki values of 539.6 and 385.2 µM. This result provided new insights for the usage of A. tsao-ko, and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates.

Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS.

Three new (1-3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and calculated ECD spectra. The NO inhibitory activities in murine microglial BV-2 cells and interactions with iNOS protein by molecular docking were evaluated for all compounds. The results showed that these compounds had potent NO inhibitory effects.

Iridoids from the roots of Valeriana jatamansi.

Two new iridoids, jatamanvaltrates N (1) and O (2), together with four known compounds (3-6), were isolated from the roots of Valeriana jatamansi. Their structures and relative configurations were elucidated by spectroscopic methods (IR, ESI-MS, HR-ESI-MS, 1D, and 2D NMR) and by comparison of their NMR spectral data with those of related compounds. All the isolated compounds were evaluated for their neuroprotective effects, and only compound 1 showed weak neuroprotective activities.

Three new guaiane-type sesquiterpenoids and a monoterpenoid from Litsea lancilimba Merr.

Three undescribed guaiane-type sesquiterpenes (1-3), and a monoterpenoid (4) along with eleven known compounds (5 - 15) were isolated from the crude extract of Litsea lancilimba Merr. The structures of all the isolated compounds were extensively elucidated on the basis of comprehensive spectroscopic techniques (HRESIMS, 1 D NMR, and 2 D NMR). Their relative and absolute configurations were comprehensively established by NOESY spectroscopy, circular dichroism (ECD) and the calculated ECD analysis. All the isolates were tested for anti-inflammatory activity by measuring the amount of nitric oxide production. Amongst tested compounds, compounds 1 - 3 exhibited moderate inhibitory activities against the production of nitric oxide with IC50 value of 35.5, 32.1, 46.7 µM in RAW264.7 cells stimulated by LPS, respectively.

Two new nor-lignans from Selaginella pulvinata (Hook. & Grev.) Maxim and their antihyperglycemic activities.

Two new nor-lignans, pulvin A (1) and moellenoside C (2), along with two known compounds (3-4) were isolated from the whole plant of Selaginella pulvinate (Hook. & Grev.) Maxim. The structures of the new compounds were established on the basis of spectroscopic data and acid hydrolysis. All the isolates were investigated for their antihyperglycemic activities in 3T3-L1 adipocytes. The results showed that compounds 1 and 2 promoted the glucose consumption prominently in 3T3-L1 adipocytes in a dose-response manner. Compound 1 and 2 induced 1.14-1.73 folds and 1.03-1.55 folds changes relative to the basal level, respectively, in the concentration range of 12.5 µM to 50 µM.

Photoredox/Hydrogen Atom Transfer Cocatalyzed C-H Difluoroallylation of Amides, Ethers, and Alkyl Aldehydes.

Herein, we report a method that combines hydrogen atom transfer and photoredox catalysis to achieve the dehydrogenative difluoroallylation of amides, ethers, and alkyl aldehydes. This operationally convenient method transforms a broad scope of substrates into the corresponding gem-difluoroalkenes via the construction of C(sp3)-C(sp3) or C(sp3)-C(sp2) bonds. Excellent functional group compatibility and high selectivity make this method have a wide range of substrate types and render it suitable for late-stage modification of pharmaceutical intermediates.

Polyoxygenated sesquiterpenoids from Salvia castanea and their potential anti-Alzheime's disease bioactivities.

Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500-3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1-6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1-6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1-9. The results showed the compounds 1-3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.

Visible-Light-Induced Deoxygenation/Defluorination Protocol for Synthesis of γ,γ-Difluoroallylic Ketones.

Herein, we describe an efficient, practical photocatalytic deoxygenation/defluorination protocol for the synthesis of γ,γ-difluoroallylic ketones from commercially available aromatic carboxylic acids, triphenylphosphine, and α-trifluoromethyl alkenes. The protocol has good functional group tolerance and a broad substrate scope. Using this method, we accomplished the late-stage functionalization of several bioactive molecules.

Amomutsaokols A-K, diarylheptanoids from Amomum tsao-ko and their α-glucosidase inhibitory activity.

Eleven undescribed diarylheptanoids, amomutsaokols A‒K (1-11), together with 13 known ones (13-24), were isolated from the active fraction of the fruits of Amomum tsao-ko. The structures of the undescribed compounds were determined by extensive 1D and 2D NMR, HRESIMS and ECD calculations. Compounds 3-5, 7, 8, 12, 14 and 19 showed obviously α-glucosidase inhibitory activity with IC50 values ranging from 12.9 to 48.8 µM. An enzyme kinetic analysis indicated that compounds 8 and 9 were α-glucosidase noncompetitive inhibitors with Ki values of 18.5 and 213.0 µM, respectively. This study supported diarylheptanoids as the active constituents of A. tsao-ko with α-glucosidase inhibitory effects.

Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

New chemical constituents from the rhizomes of Sparganium stoloniferum.

A new sucrose ester named beta-D-(1-O-acetyl-3-O-cis-feruloyl)fructofuranosyl alpha-D-2',3',6'-O-triacetylglucopyranoside 1 and a novel phenylpropanoid glycerol named 1-O-cis-feruloyl-3-O-trans-p-coumaroylglycerol 2, have been isolated from Sparganium stoloniferum. Their structures were elucidated by spectroscopic methods.

Two new stilbenoids from Pleione bulbocodioides.

Two new stilbenoids, 9-(4'-hydroxy-3'-methoxyphenyl)-10-(hydroxymethyl)-11-methoxy-5,6,9,10-tetrahydrophenanthro[2,3-b]furan-3-ol and 2-(4''-hydroxybenzyl)-3-(3'-hydroxyphenethyl)-5-methoxy-cyclohexa-2,5-diene-1,4-dione, together with the three known stilbenoids were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structures were elucidated by spectroscopic methods.

A novel sesquiterpene from the roots of Vladimiria souliei.

A novel sesquiterpene lactone, 1beta, 14-peroxy-4alpha-hydroxy-5alphaH, 7alphaH,6betaH-eudesm-11(13)-en-6, 12 olide (1), was isolated from the roots of Vladimiria souliei. The structure was elucidated by spectroscopic methods.

Hydrophilic quaternary ammonium-group-containing [FeFe]H2ase models prepared by quaternization of the pyridyl N atoms in pyridylazadiphosphine- and pyridylmethylazadiphosphine-bridged diiron complexes with various electrophiles.

The first aromatic quaternary ammonium-group-containing [FeFe]H2ase models have been prepared by a simple and convenient two-step method in high yields. Thus, on the basis of preparation of the N-pyridylazadiphosphine-bridged diiron complex (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NC5H4N] (A) by CO substitution of parent complex (µ-PDT)Fe2(CO)6 with N-pyridylazadiphosphine 3-(Ph2P)2NC5H4N in refluxing xylene, further quaternization of the pyridyl N atom in complex A with electrophile 1,3-propanesultone, 1,3,2-dioxathiolane-2,2-dioxide, or 4-bromobutyric acid in refluxing MeCN afforded the pyridyl quaternary ammonium-group-containing models (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NC5H4NR] (1, R = (CH2)3SO3; 2, R = (CH2)2OSO3) and (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NC5H4N(CH2)3CO2H]Br (3). Similarly, the N-pyridylmethylazadiphosphine-bridged diiron complex (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NCH2C5H4N] (B) could be prepared by CO substitution of parent complex (µ-PDT)Fe2(CO)6 with N-pyridylmethylazadiphosphine 3-(Ph2P)2NCH2C5H4N in refluxing xylene, while further quaternization of the pyridylmethyl N atom in complex B with 1,3-propanesultone and 3-bromo-1-propanol in MeCN at reflux resulted in formation of the pyridylmethyl quaternary ammonium-group-containing models (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NCH2C5H4N(CH2)3SO3] (4) and (µ-PDT)Fe2(CO)4[µ-3-(Ph2P)2NCH2C5H4N(CH2)3OH]Br (5), respectively. All new complexes A, B, and 1-5 were characterized by elemental analysis and various spectroscopies, while the molecular structures of complexes A, B, 2 and 5 were further confirmed by X-ray crystallography. The electrochemical study on hydrophilic models 1 and 3 in MeCN and the MeCN/H2O mixed solvent indicated that the reduction potentials were shifted to less-negative potentials as the water content increased; such an observation implies that both 1 and 3 are easily reduced in the mixed MeCN/H2O solvent than in MeCN. In addition, the electrocatalytic study demonstrated that both 1 and 3 can serve as electrocatalysts for H2 production from acetic acid with higher icat/ip and TONs in MeCN/H2O than in MeCN.

Cytotoxic sesquiterpenoids from the ethanol extract of fruits of Celastrus orbiculatus.

AIM OF THE STUDY: To investigate the cytotoxic compounds against human melanoma A375-S2 and human cervical carcinoma Hela cell lines from the fruits of Celastrus orbiculatus. MATERIALS AND METHODS: The ethanol extract of the fruits of C. orbiculatus was found to exhibit significant cytotoxic activity. After partition, the column chromatography and Semi-preparative HPLC were used for activity guided fractionation from the active petroleum ether-soluble part. NMR and ESI-MS spectra for structure analysis were recorded on spectrometers, respectively. The cytotoxic activities of the isolated compounds were determined using the MTT assay. RESULTS: Four sesquiterpenoids (1-4) were isolated by activity guided fractionation from the ethanol extract of the fruits of C. orbiculatus. Compounds 1-3 exhibited promising cytotoxicities against the Hela cells and A375-S2 cells. The cytotoxic activities of compounds 1-3 seemed to be dose-dependent, which exhibited more potent inhibition for the proliferation of two cell lines when increased the concentrations of every compounds. Among these compounds, compound 2 showed most cytotoxicities against either Hela cells or the A375-S2 cells. CONCLUSIONS: The cytotoxic activity of the ethanol extract of fruits of C. orbiculatus against human melanoma A375-S2 and human cervical carcinoma Hela cells due to its content of sesquiterpenoids, supports its potential therapeutic value for the treatment of tumor.

Cytotoxic beta-dihydroagarofuran sesquiterpenoids from the fruits of Celastrus orbiculatus.

Assay-guided fractionation led to the isolation of nine beta-dihydroagarofuran sesquiterpenoids from the fruits of Celastrus orbiculatus. All isolated beta-dihydroagarofuran sesquiterpenoids were tested for their cytotoxic activity against human melanoma A375-S2 and human cervical carcinoma Hela cell lines. Among them, compounds 1-5 and 7 showed cytotoxic activity. Compound 3 exhibited promising cytotoxicity against both human melanoma A375-S2 and human cervical carcinoma Hela cell lines. The structure-activity relationship was discussed briefly.

[Studies on chemical constituents of Ranunculus ternatus].

OBJECTIVE: To study the active constituents of Ranunculus ternatus. METHOD: The constituents were isolated with silica gel and Sephadex LH -20 gel column chromatography and purified by HPLC. Their structures were elucidated by spectroscopy. RESULT: Sixteen compounds were obtained and identified as Stigmasta4, 6, 8 (14), 22-tetraen-3-one (1), 5-hydroxymethyl furaldehyde (2), gamma-keto-delta-valerolactone (3), pantolactone (4), 5-hydroxymethyl-dihydro-furan-2-one (5), methyl 5-hydroxy-4-oxopentanoate (6), methyl hydrogen succinate (7), succinic acid monoethyl ester (8), 3, 4-dihydroxybenzoic acid methyl ester (9), p-hydroxycinnamic acid (10), 4-oxo-pentanoic acid (11), succinic acid (12), nonanedioic acid (13), 4-hydroxybenzoic acid (14), 4-hydroxybenzaldehyde (15), stigmasterol-3-O-beta-D-glucopyranoside (16). CONCLUSION: Compound 1, 4 -15 are obtained from this plant for the first time.

Synthesis, characterization, and H/D exchange of µ-hydride-containing [FeFe]-hydrogenase subsite models formed by protonation reactions of (µ-TDT)Fe2(CO)4(PMe3)2 (TDT = SCH2SCH2S) with protic acids.

As [FeFe]-hydrogenase models, the first thiodithiolate (TDT) ligand-containing µ-hydride complexes [(µ-TDT)Fe2(CO)4(PMe3)2(µ-H)](+)Y(-) (2-7, Y = Cl, ClO4, PF6, BF4, CF3CO2, CF3SO3) have been prepared by protonation reactions of (µ-TDT)Fe2(CO)4(PMe3)2 (1) with the corresponding HY acids. While the protonation reactions are monitored by in situ(1)H and (31)P{(1)H} NMR spectroscopy to show the isomer type and stability of 2-7, the structures of the isolated 2-7 are characterized by elemental analysis, spectroscopy and for some of them by X-ray crystallography. Although the H/D exchange of µ-hydride complex 7 (Y = CF3SO3) with D2 or D2O has been proved not to occur under the studied conditions, the H/D exchange of 7 with DCl gives the µ-deuterium complex [(µ-TDT)Fe2(CO)4(PMe3)2(µ-D)](+)[CF3SO3](-) (8) in a nearly quantitative yield. To our knowledge, 8 is the first crystallographically characterized µ-deuterium-containing butterfly [2Fe2S] complex produced by H/D exchange reaction.