Inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells by lignans isolated from Euonymus alatus leaves and twigs

The 80% methanolic extract of Euonymus alatus leaves and twigs afforded three new lignans, (−)-threo-4,9,4′,9′-tetrahydroxy-3,7,3′,5′-tetramethoxy-8-O-8′-neolignan (1), (−)-threo-4,9,4′,9′-tetrahydroxy-3,5,7,3′-tetramethoxy-8-O-8′-neolignan (2), (7R,8R,7′R)-(+)-lyoniresinol (3), together with seventeen known lignans (4-20). The structures of 1-20 were elucidated by extensive 1D and 2D spectroscopic methods including ¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMQC, HMBC and NOESY. All the isolated compounds except for dilignans (19 and 20) significantly inhibited nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells.     

Chemical constituents of Picea neoveitchii

Four flavonoids, 5,7,4′-trihydroxy-3,8,-dimethoxy-6-C-methylflavone (1), 5,8,4′-trihydroxy-3,7-dimethoxy-6-C-methylflavone (2), 7-methoxy-6-C-methylkaempferol (3) and kaempferol-7-O-(2″-E-p-coumaroyl)-α-l-arabinofuranoside (4), together with 15 known compounds, were isolated from the twigs and leaves of Picea neoveitchii Mast. Their structures were elucidated on the basis of analyses of spectroscopic data. Compound 4 showed strong anti-fungal activity against Fusarium oxysporum whereas compounds 1-4 were all active against Rhizoctonia solani.     

Synthesis of regioisomeric 17β-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

The reaction of 3β-hydroxy-21-hydroxymethylidenepregn-5-en-3β-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17β-(1-phenyl-3-pyrazolyl)androst-3-en-3β-ol (5a) and 17β-(1-phenyl-5-pyrazolyl)androst-5-en-3β-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3β-hydroxy-17β-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Δ⁴-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC₅₀) of these compounds on rat testicular C_17,20-lyase were investigated by means of an in vitro radioligand incubation technique.     

New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights

Bioassay-guided extraction of the stem bark of Knema laurina showed the acetylcholinesterase (AChE) inhibitory activity of DCM and hexane fractions. Further repeated column chromatography of hexane and DCM fractions resulted in the isolation and purification of five alkenyl phenol and salicylic acid derivatives. New compounds, (+)-2-hydroxy-6-(10′-hydroxypentadec-8′(E)-enyl)benzoic acid (1) and 3-pentadec-10′(Z)-enylphenol (2), along with known 3-heptadec-10′(Z)-enylphenol (3), 2-hydroxy-6-(pentadec-10′(Z)-enyl)benzoic acid (4), and 2-hydroxy-6-(10′(Z)-heptadecenyl)benzoic acid (5) were isolated from the stem bark of this plant. Compounds (1-5) were tested for their acetylcholinesterase inhibitory activity. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and chemical derivatizations. Compound 5 showed strong acetylcholinesterase inhibitory activity with IC₅₀ of 0.573 ± 0.0260 μM. Docking studies of compound 5 indicated that the phenolic compound with an elongated side chain could possibly penetrate deep into the active site of the enzyme and arrange itself through π-π interaction, H-bonding, and hydrophobic contacts with some critical residues along the complex geometry of the active gorge.     

Isoprenylated cyclohexanoids from the basidiomycete Hexagonia speciosa

Nine oxygenated cyclohexanoids, speciosins L-T (1-9) as well as a 5H-furan-2-one metabolite, 5′-O-acetylaporpinone A (10), together with known analogs, speciosins A, B, D, E, F, I and K (11-17), and aporpinone A (18), were isolated from a scale-up cultures of the basidiomycete Hexagonia speciosa. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR. Speciosin B (12) showed significant cytotoxicity against several tumor cell lines with IC₅₀ values in the range 0.23-3.30 μM.     

Iridoids from Gentiana loureirii

Iridoid glycosides, 2′,3′,6′-tri-O-acetyl-4′-O-trans-p-(O-β-d-glucopyranosyl)coumaroyl-7-ketologanin (1), 2′-O-caffeoylloganic acid (2), 2′-O-p-hydroxybenzoylloganic acid (3), 2′-O-trans-p-coumaroylloganic acid (4), and 2′-O-cis-p-coumaroylloganic acid (5), were isolated from whole plants of Gentiana loureirii along with six known iridoids, 7-ketologanin (6), loganin (7), loganic acid (8), sweroside, boonein, and isoboonein, and three other known compounds. Their structures were elucidated by spectroscopic means and chemical correlations. The isolated iridoids were evaluated for antibacterial and antioxidant activities, but were either inactive or very weakly active.     

Anti-inflammatory activity of constituents from Glechoma hederacea var. longituba

Rosmarinic acid, its analogues, and a phenolic compound were obtained from G. hederacea var. longituba. There were two new compounds, methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (1) and benzyl-4′-hydroxy-benzoyl-3′-O-β-d-glucopyranoside (4), and four known compounds (2, 3, 5 and 6). The structures of these compounds were determined on the basis of spectroscopic methods. Each compound was tested by NF-κB luciferase assay and three rosmarinic acid analogues inhibited NF-κB production and the induction of COX-2 and iNOS mRNA in HepG2 cells.     

Steroids from the leaves of Chinese Melia azedarach and their cytotoxic effects on human cancer cell lines

Three new (1-3) and several known (4-6) steroids were isolated from the leaves of Chinese Melia azedarach. The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR techniques and mass spectrometry to be (20S)-5,24(28)-ergostadiene-3β,7α,16β,20-tetrol (1), (20S)-5-ergostene-3β,7α,16β,20-tetrol (2), and 2α,3β-dihydro-5-pregnen-16-one (3). The cytotoxicities of the isolated compounds against three human cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and (20S)-5-stigmastene-3β,7α,20-triol (4) were found to show significant cyctotoxic effects with IC₅₀s from 12.0 to 30.1 μg/mL.     

Ecdysteroids from Polypodium vulgare L

Three new compounds (3, 7, and 11) together with eight known phytoecdysteroids (1, 2, 4-6, and 8-10) were isolated from the rhizomes of common polypody, Polypodium vulgare L. The structures of compounds were elucidated by spectroscopic methods including 1D and 2D NMR measurements. The ¹H and ¹³C NMR assignments of compounds 1, 6, 9 and 10 are included.     

Osteogenic activity of diphenyl ether-type cyclic diarylheptanoids derived from Acer nikoense

Osteogenic activity of six diarylheptanoids, acerogenin A (1), (R)-acerogenin B (2), aceroside I (3), aceroside B₁ (4), aceroside III (5) and (−)-centrolobol (6) and two phenolic compounds; (+)-rhododendrol (7) and (+)-cathechin (8), isolated from the stem bark of Acer nikoense (Nikko maple) was evaluated using alkaline phosphatase (ALP) activity as a marker for early osteoblast differentiation. We found that the diphenyl ether-type cyclic diarylheptanoids 1-5 promoted ALP activity in mouse preosteoblastic MC3T3-E1 cells without affecting cell proliferation, but linear-type diarylheptanoid 6 and phenolic compounds 7 and 8 did not. Diphenyl ether-type cyclic diarylheptanoids 1-4 also increased protein production of osteocalcin, a late stage maker for osteoblast differentiation, and induced osteoblastic mineralization. Structure-activity relationships of these compounds demonstrated that the stimulative efficacy of aglycones was higher than that of its glycosides. Taken together, diphenyl ether-type cyclic diarylheptanoids promote early- and late-stage osteoblastogenesis, which may open the possibility for the development of novel osteogenic agents.     

Biological evaluation of phenolic constituents from the trunk of Berberis koreana

A bioassay-guided fractionation and chemical investigation of the trunk of Berberis koreana resulted in the isolation and identification of a new sesquilignan, named berbikonol (1), along with fourteen known lignan derivatives (2-15) and a new phenolic compound, named berfussinol (16), together with five known ones (17-21). The structures of these new compounds were elucidated on the basis of 1D and 2D NMR spectroscopic data analysis as well as circular dichroism (CD) spectroscopy studies. Compounds 1-5, 7-8, 11, and 14 showed significant cytotoxicity against the XF498 cell line with IC₅₀ values of 7.14-19.32 μM. In addition, compounds 3-8 and 15 strongly reduced nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglial cell line.     

Flavones and flavone glycosides from Halophila johnsonii

Halophila johnsonii Eiseman is a shallow-water marine angiosperm which contains UV-absorbing metabolites. Studies on methanol extracts of H. johnsonii by means of HPLC-UV, NMR, HPLC-MS resulted in isolation and identification of seven previously unknown flavone glycosides: 5,6,7,3′,4′,5′-hexahydroxyflavone-7-O-β-glucopyranoside (1), 5,6,7,3′,4′,5′-hexahydroxyflavone-7-O-(6″-O-acetyl)-β-glucopyranoside (2), 6-hydroxyluteolin-7-O-(6″-O-acetyl)-β-glucopyranoside (3), 6-hydroxyapigenin-7-O-(6″-O-acetyl)-β-glucopyranoside (4), 6-hydroxyapigenin-7-O-(6″-O-[E]-coumaroyl)-β-glucopyranoside (5), 6-hydroxyapigenin-7-O-(6″-O-[E]-caffeoyl)-β-glucopyranoside (6) and 6-hydroxyluteolin-7-O-(6″-O-[E]-coumaroyl)-β-glucopyranoside (7). Also isolated were three known flavone glycosides, 6-hydroxyluteolin 7-O-β-glucopyranoside (8), scutellarein-7-O-β-glucopyranoside (9), and spicoside (10), and five known flavones, pedalitin (11), ladanetin (12), luteolin (13), apegenin (14) and myricetin (15). Qualitative comparison of the flavonoid distribution in the leaf and rhizome-root portions of the plant was also investigated, with the aim of establishing the UV-protecting roles that flavonoids played in the sea grass.     

Potential defense-related prenylated isoflavones in lactofen-induced soybean

An integrated LC-MS and NMR metabolomic study was conducted to investigate metabolites whose formation was induced by lactofen (1), a soybean (Glycine max L.) disease resistance-inducing herbicide. First, LC-MS analyses of control and lactofen (1)-induced soybean extracts were performed. The LC-MS raw data were then processed by a custom designed bioinformatics program to detect the induced metabolites so formed. Finally, structures of unknown induced metabolites were determined on the basis of their 1D and 2D NMR spectroscopic data. Structure of two previously unreported compounds, 7,8-dihydroxy-4′-methoxy-3′-prenylisoflavone (2) and 7-hydroxy-4′,8-dimethoxy-3′-prenylisoflavone (3) were elucidated together with four known prenylated compounds, 3′-prenyldaidzein (4), 8-prenyldaidzein (5), 3′-prenylgenistein (6), and 4-prenylcoumestrol (7). Compounds (2-6) are reported for the first time in soybean, as are the ¹³C chemical shift assignments for compound (7). Formation of these six prenylated compounds was also induced by the primary defense glucan elicitor from the cell wall of the pathogen Phytophthora sojae (Kauf. and Gerde.), further suggesting a potential role in soybean defense. These results highlight the metabolic flexibility within soybean secondary product pathways and suggest that prenylation may be associated with defense responses. Moreover, this study demonstrates a promising future approach using metabolomics on elicitor-induced plants for discovery of unknown compounds even in relatively well studied plants.     

Saponins and a lignan derivative of Terminalia tropophylla from the Madagascar Dry Forest

A study of an EtOH extract obtained from the roots of the Madagascan plant Terminalia tropophylla H. Perrier (Combretaceae) led to isolation of the oleanane-type triterpenoid saponin 1, the lignan derivative 2, and the two known saponins arjunglucoside I (3) and sericoside (4). The structures of compounds 1 (terminaliaside A) and 2 (4′-O-cinnamoyl cleomiscosin A) were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compound 1 showed antiproliferative activity against the A2780 human ovarian cancer cell line with an IC₅₀ value of 1.2 μM.     

Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC₅₀ values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7′ might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments.     

Withanolides from Withania aristata and their cytotoxic activity

Seven new withanolides (1-7), along with three known ones (8-10), were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 2D NMR experiments and spectrometric techniques, and the absolute configuration of 1 and 2 was established by CD analysis. In the search for new cytotoxic compounds from Withania species, the isolated compounds 1-9, along with two derivatives, were assayed for their cytotoxicity against HeLa, MCF-7 and A-549 human tumor cell lines. Derivative (4S,20R,22R)-27-acetoxy-4-p-bromobenzoyloxy-1-oxo-witha-2,5,16,24-tetraenolide (13) showed cytotoxicity against all the cell lines assayed with IC₅₀ values ranging from 2.8 to 3.6 μM, and (4S,20R,22R)-4,27-diacetoxy-4-hydroxy-1-oxo-witha-2,5,16,24-tetraenolide (12) exhibited an IC₅₀ value of 5.4 μM on the MCF-7 cell line.     

Non-cannabinoid constituents from a high potency Cannabis sativa variety

Six new non-cannabinoid constituents were isolated from a high potency Cannabis sativa L. variety, namely 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone (1), 4,5-dihydroxy-2,3,6-trimethoxy-9,10-dihydrophenanthrene (2), 4-hydroxy-2,3,6,7-tetramethoxy-9,10-dihydrophenanthrene (3), 4,7-dimethoxy-1,2,5-trihydroxyphenanthrene (4), cannflavin C (5) and β-sitosteryl-3-O-β-d-glucopyranoside-2′-O-palmitate (6). In addition, five known compounds, α-cannabispiranol (7), chrysoeriol (8), 6-prenylapigenin (9), cannflavin A (10) and β-acetyl cannabispiranol (11) were identified, with 8 and 9 being reported for the first time from cannabis. Some isolates displayed weak to strong antimicrobial, antileishmanial, antimalarial and anti-oxidant activities. Compounds 2-4 were inactive as analgesics.     

β-Diiminatolanthanoid(III) halides revisited

The crystalline compounds [LnCl₂(L)(thf)₂] [Ln = Ce (1), Tb (2), Yb (3)], [NdI₂(L)(thf)₂] (4), [LnCl(L′)₂] [Ln = Tb (5), Yb (6) (a known compound)] and [YbCl(L′′)(μ-Cl)₂Li(OEt₂)₂] (7) have been prepared [L = {N(C₆H₃Prⁱ₂-2,6)C(H)}₂CPh, L′ = {N(SiMe₃)C(Ph)}₂CH, L′′ = {N(SiMe₃)C(C₆H₄Ph-4)}₂CH]. The X-ray molecular structures of 2-7 have been established; in each, the monoanionic ligand L, L′ or L′′ is N,N′-chelating and essentially π-delocalised. Each of 1-7 was prepared from the appropriate LnCl₃, or for 4 [NdI₃(thf)₂], and an equivalent portion of the appropriate alkali metal [Li for 7, Na for 2, 3 and 5, or K for 1, 4 and 6] β-diiminate in thf; the isolation of exclusively 5 and 6 (rather than the L′ analogues of 2 or 3) is noteworthy, as is the structure of 7 which has no precedent in Group 3 or 4f metal β-diiminato chemistry.     

Antioxidant activity of a new C-glycosylflavone from the leaves of Ficus microcarpa

By bioactive-guided fractionation of methanol extract of the Ficus microcarpa leaves, one new C-glucosylflavone, ficuflavoside (1), one new megastigmane glycoside, ficumegasoside (8), and twelve known compounds including flavonoids (2-6), phenylpropanoids (7), megastigmanes (9-11) and sterol derivatives (12-14) were isolated. Their chemical structures were elucidated by mass, 1D, and 2D NMR spectroscopies. The antioxidant activities of these compounds were measured using the oxygen radical absorbance capacity methods. Compounds 1-6 exhibited potent antioxidant activities of 6.6-9.5 μM Trolox equivalents at the concentration of 2.0 μM. The results indicated 2, 3, and 5 having meaningful reducing capacity of copper (I) ions concentration of 6.1-8.4 μM.     

A new iridoid and effect on the rat aortic vascular smooth muscle cell proliferation of isolated compounds from Buddleja officinalis

A new iridoid, named methylscutelloside (1) together with 19 known compounds belonging to the iridoids (2-4), monoterpenoids (5), flavonoids (6-8), triterpenoids (9-14), and phenylethanoids (15-20) were isolated from the flowers of Buddleja officinalis. Their chemical structures were elucidated on the basis of physicochemical properties, and by spectroscopic methods including 1D, 2D NMR, and MS. All isolated compounds were tested in vitro for their effects on the proliferation of rat aortic vascular smooth muscle cells (VSMCs). Among them, iridoids were the main active components and showed significant inhibitory effects on PDGF-BB-induced proliferation in rat aortic VSMCs.