Pyranocoumarins from Glehnia littoralis inhibit the LPS-induced NO production in macrophage RAW 264.7 cells

A new dihydropyranocoumarin, (+)-cis-(3′S,4′S)-diisobutyrylkhellactone (1), together with five known compounds, 3′-senecioyl-4′-acetylkhellactone (2), 3′-isovaleryl-4′-acetylkhellactone (3), 3′,4′-disenecioylkhellactone (4), 3′-isovaleryl-4′-senecioylkhellactone (5), and 3′,4′-diisovalerylkhellactone (6), was isolated from Glehnia littoralis. Their chemical structures were elucidated based on the spectroscopic data interpretation, particularly 1D and 2D NMR data including HMQC and HMBC. All the isolated compounds showed the potential to inhibit LPS-induced nitric oxide production in RAW 264.7 cells with IC₅₀ values ranging from 7.4 to 44.3 μM.     

New flavonoids from the fruits of Cornus mas,Cornaceae

One new β-hydroxychalcone, 4-acetoxy-5,2′,4′,6′,β-pentahydroxy-3-methoxychalcone (1), one new flavanone, 7,3′-dihydroxy-5,4′-dimethoxyflavanone (2) and seven known compounds, 2R, 3R-trans-aromadendrin (3), naringenin-7-O-methylether (4), myricetin (5), quercetin-3-O-rutinoside (6), ursolic acid (7), gallic acid (8) and d-glucose (9) were isolated from the methanolic fruit extract of Cornus mas L. (=Cornus mascula L.), Cornaceae. The structures of the new compounds were elucidated on the basis of extensive spectroscopic methods, including 2D NMR experiments and of known compounds by comparison of physical and spectral data with literature.     

Lignan glycosides from the Rhizomes of Smilax trinervula and their Biological activities

Phytochemical investigation of the rhizomes of Smilax trinervula led to isolation and structure elucidation of eight lignan glycosides, including five new lignans, namely, (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4′-O-β-d-glucopyranoside (1), (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4-O-β-d- glucopyranoside (2) (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-4′, 7-epoxy-8, 5′-neolignan 9′-O-β-d-glucopyranoside (3), (7R, 8R)-4, 9, 9′-trihydroxy-3, 5-dimethoxy-7.O.4′, 8.O.3′- neolignan 9′-O-β-d-glucopyranoside (4), and (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-8, 4′-oxy-neolignan 4-O-β-d-glucopyranoside (5), along with three known compounds (6-8). Their structures were established mainly on the basis of 1D and 2D NMR spectral data, ESI–MS and comparison with the literature. Compounds 1-8 were tested in vitro for their cytotoxic activity against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Compounds 3 and 5 exhibited cytotoxic activity against Lovo cells, with IC₅₀ value of 10.4 μM and 8.5 μM, respectively.     

Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells

A new coumarin, (?)-cis-(3′R,4′R)-4′-O-angeloylkhellactone-3′-O-β-d-glucopyranoside (1) and two new chalcones, 3′-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2′,4′-trihydroxychalcone (4) and (±)-4,2′,4′-trihydroxy-3′-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3′-O-methylvaginol (3), (?)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6–9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1–9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress.     

New metabolites from the alga-derived fungi Penicillium thomii Maire and Penicillium lividum Westling

A new meroterpenoid, austalide H acid ethyl ester (1), 5-(2′,4′-dihydroxy-6′-methylphenyl)-3-methylfuran-2-carboxylic acid (2), 5-(2′-hydroxy-6′-methylphenyl)-3-methylfuran-2-carboxylic acid (3) and 5-((6′-methyl-4′-oxo-3′,4′-dihydro-2H-pyran-2′-yl)methyl)-3-methylfuran-2-carboxylic acid (4), along with six known compounds, austalides H, J, K, and P (5–8), questin (9) and sulochrin (10) were isolated from the lipophilic extract of the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. The structures of the isolated compounds were determined based on spectroscopic methods. The austalides showed significant inhibitory activity against endo-1,3-β-d-Glucanase from a crystalline stalk of the marine mollusk Pseudocardium sachalinensis.     

Two new antioxidant flavones from the twigs of Eriosema robustum (Fabaceae)

Phytochemical study of the ethanol extract of the twigs of Eriosema robustum, a Cameroonian medicinal plant resulted to the isolation of two new flavones, 2′,3′,5′,5,7-pentahydroxy-3,4′-dimethoxyflavone (1) and 2′,3,5′,5,7-pentahydroxy-4′-methoxyflavone (2), along with five known compounds: 6-prenylpinocembrin (3), 1-O-heptatriacontanoyl glycerol (4), β-sitosterol (5), stigmasterol (6) and 3-O-β-d-glucopyranoside of sitosterol (7). The structure of the isolated compounds were elucidated on the basis of their NMR, UV and MS data, and by comparison with those reported in the literature. The ethanol crude extract, fractions and some isolated compounds (1–4) were evaluated for their radical scavenging capacity using 2,2-diphenyl-1-picryhydrazyl (DPPH). The crude extract, fraction II, the new compounds namely robusflavones A (1) and B (2) exhibited significant antioxidant activity.     

Prenylflavone derivatives from Broussonetia papyrifera,inhibit the growth of breast cancer cells in vitro and in vivo

Two new prenylflavones 5,7,3′,4′-tetrahydroxy-3-methoxy-8-geranylflavone (1) and 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone (2), as well as four known ones, uralenol (3), papyriflavonol A (4), broussoflavonol B (5) and broussochalcone A (6) were isolated and purified from an ethyl acetate-soluble extract of the barks of Broussonetia papyrifera. Their structures were determined with the spectroscopic methods including HR-EI-MS, 1D and 2D NMR. We found that compounds 2–6 showed potent anti-proliferation effects on ER-positive breast cancer MCF-7 cells in vitro. The IC₅₀ values of compounds 2 and 5 were 4.41 and 4.19 μM respectively after the treatment of 72 h. We also found that compounds 2 and 5 strongly down-regulated expression concentrations of estrogen receptor-α (ER-α) and were able to inhibit tumor growth in a xenograft model of the human breast cancer line BCAP-37 in vivo. Our results demonstrated that prenylflavones from B. Papyrifera exhibit potent anti-tumor activity.     

Chemical constituents from Oncocalyx glabratus and their biological activities

Chemical investigation of the aerial parts of Oncocalyx glabratus resulted in the isolation of three new flavan derivatives, 5,3′,4′-trihydroxyflavan 7-O-gallate (1), 5,4′-dihydroxyflavan 7-3′-O-digallate (2) and 5,3′-dihydroxyflavan 7-4′-O-digallate (3), named oncoglabrinol A, B and C, respectively, together with four known flavonols, (+)-catechin (4), (+)-catechin-7-O-gallate (5), catechin-7-4′-O-digallate (6A) and catechin-7-3′-O-digallate (6B). The structures of the compounds were established by 1D, 2D NMR and ESI-HRMS spectral analyses. The biological activity of the compounds was tested through a series of in vitro assays designed for determining cytotoxicity, antiviral activity against hepatitis B virus, and antidiabetic activity. All compounds were found non-toxic and showed moderate anti-HBV activity. Compounds 3 and 6 showed dual PPAR agonistic activity while others were not effective.     

Isoflavones from the roots and stems of Nicotiana Tabacum and their anti-tobacco mosaic virus activities

Two new isoflavones, 7-hydroxy-6,3′,4′,5′-tetramethoxy-isoflavone (1) and 6-hydroxy-7,3′,4′,5′-tetramethoxy-isoflavone (2), together with seven known isoflavones were isolated from the roots and stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS, extensive 1D and 2D NMR spectroscopic studies and chemical evidences. The anti-tobacco mosaic virus (anti-TMV) activities of the isoflavones were also evaluated. The results reveal that compound 9 shows high anti-TMV activity, compound 2 shows moderate anti-TMV activity, and compounds 1, 3–8 show weak anti-TMV activities.     

Antiproliferative constituents from Aphananthe aspera leaves

Extensive screening for the antiproliferative activity of different compounds found in trees was performed by extracting the leaves of Aphananthe aspera (Thunb.) Planch and then using chromatographic separation to afford 2 new compounds, (2S,4R)-2-carboxy-4-(E)-p-caffeoyl-1-methyl-hydroxyproline (1) and 5-O-caffeoyl quinic acid-(7′R,8′S,7′′E)-3′,4′,3′′-dihydroxy-4′′,7′-epoxy-8′,5′′-neolign-7′-ene-9- carboxyl (2). In addition, 6 known compounds were discovered from the leaves of this plant. The structural determination of all compounds, including their absolute configurations, was established by UV, IR, HRESIMS, 1D and 2D NMR, and CD spectroscopy. The novel compound 1 showed strong antiproliferative activity against human breast adenocarcinoma cells MCF-7 and MDA-MB-231.     

Phytochemical and chemotaxonomic study on Piper pleiocarpum Chang ex Tseng

The phytochemical study of Piper pleiocarpum Chang ex Tseng led to the isolation of eighteen compounds (1–18), including ten lignanoids, galbelgin (1), (+) sesamin (2), denudatin A (3), hancinone (4), (7S,8S, 3′R)-Δ^8'-3,3′,4-trimethoxy-3′,6′-dihydro-6′-oxo-7.0.4′,8.3′-lignan[(2S,3S,3aR)-2-(3,4-dimethoxyphenyl)-3,3a-dihydro-3a-methoxy-3-methyl-5-(2-propenyl)-6(2H))-benzofuranone] (5), (−)-(7R,8R)-machilin D (6), (1R,2R)-2-[2-methoxy-4-((E)-prop-1-enyl)phenoxy]-1-(3,4-dimethoxyphenyl)propyl acetate (7), piperbonin A (8), machilin D (9), 4-methoxymachilin D (10), one amide alkaloid, Δ^α,β-dihydropiperine (11), six polyoxygenated cyclohexenes, ent-curcuminol F (12), uvaribonol E (13), ellipeiopsol A (14), 1S,2R,3R,4S-1-ethoxy-2-[(benzoyloxy)methyl]cyclohex-5-ene-2,3,4-triol, 3-acetate (15), (+)-crotepoxide (16), (+)-senediol (17), and one benzoate derivative, 2-acetoxybenzyl benzoate (18). Their structures were established by spectroscopic data and by comparison with the literature. All the compounds were firstly isolated from P. pleiocarpum, while ten compounds 6–7, 9–10, 12–15, 17–18 were isolated from the genus Piper and the family Piperaceae for the first time. The chemotaxonomic significance of these compounds was also discussed. The isolation of compounds 6–7, 9–10 may be used as chemotaxonomic markers for the genus of Piper.     

Three new benzophenone glycosides with MAO-A inhibitory activity from Hypericum thasium Griseb.

Purification of n-BuOH fraction from 80% ethanol extract of Hypericum thasium Griseb. resulted in the isolation of three new compounds 3′,4,5′-trihydroxy-6-methoxy-2-O-α-l-arabinosylbenzophenone (1), 3′,4,5′,6-tetrahydroxy-2-O-α-l-arabinosylbenzophenone (2), and 3′,4-dihydroxy-5′-methoxy-2-O-α-l-arabinosyl-6-O-β-d-xylosylbenzophenone (3) along with a known flavonoid glycoside quercetin-3-O-α-l-arabinofuranoside (4). The structures of the new compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds (1–4), as well as quercetin, and kaempferol previously isolated from EtOAc fraction were screened against MAO-A inhibitory activity. When tested against the MAO-A quercetin and kaempferol displayed IC₅₀ values of 19.6, and 17.5 μM, respectively. The IC₅₀ values for MAO-A inhibition by compounds (1–4) were 310.3, 111.2, 726.0, and 534.1 μM, respectively. Standard inhibitor (clorgyline) exhibited MAO-A inhibition with an IC₅₀ value of 0.5 μM.     

Five new iridoïd dimers from the fruits of Canthium subcordatum DC (syn. Psydrax subcordata DC)

Five new iridoid dimers, canthiumosides 1–5 (1–4 and 5a), together with nine known compounds, shanzhigenin methyl ester (6), 1-epishanzhigenin methyl ester (6′), linearin (7), 1-epilinearin (7′), mussaenoside (8), shanzhiside methyl ester (9), 3′,4′,7-trihydroxyflavone (10), betulinic acid (11), and oleanolic acid (12) were isolated from the fruits of Canthium subcordatum DC (Syn. Psydrax subcordata (DC) Bridson). The structures of these compounds were established by interpretation of their spectral data, mainly HR-TOFESIMS, 1D NMR (¹H, ¹³C and DEPT) and 2D NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY), and by comparison with the literature.     

Benzophenones and xanthones from Garcinia cantleyana var. cantleyana and their inhibitory activities on human low-density lipoprotein oxidation and platelet aggregation

Three benzophenones, 2,6,3′,5′-tetrahydroxybenzophenone (1), 3,4,5,3′,5′-pentahydroxybenzophenone (3) and 3,5,3′,5′-tetrahydroxy-4-methoxybenzophenone (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3′-methyl-2′-oxo-but-3′-enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var. cantleyana. Eight known compounds, 3,4,5,3′-tetrahydroxy benzophenone (2), 1,3,5-trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3β-ol and friedelin were also isolated. The structures of the compounds were elucidated by spectroscopic methods. The compounds were investigated for their ability to inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human whole blood in vitro. Most of the compounds showed strong antioxidant activity with compound 8 showing the highest inhibition with an IC₅₀ value of 0.5 μM, comparable to that of probucol. Among the compounds tested, only compound 4 exhibited strong inhibitory activity against platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5 and 8 showed selective inhibitory activity on platelet aggregation induced by ADP.     

New derivatives from the aerial parts of Boerhaavia diffusa L. (Nyctaginaceae)

Boerhaavia diffusa L. is used in the traditional medicine of several Asian countries. The isolation and identification of five new compounds, together with 11 known compounds, from the ethyl acetate extract of the aerial part of B. diffusa grown Vietnam is reported. The structure of the new compounds was established by 1D and 2D NMR spectroscopy, and high resolution ESI-MS analysis. New compounds are two rotenoids: 9,11-dihydroxy-6,10-dimethoxy[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one (boeravinone P, 3) and 3-[2-(β-d-glucopyranosyloxy)-3-hydroxyphenyl]-5-hydroxy-2-hydroxymethyl-7-methoxy-6-methyl-4H-1-benzopyran-4-one (boeravinone Q, 9), an atropisomeric mixture of two rotenoid glycosides (3′,5-dihydroxy-2-hydroxymethyl-7-methoxy-6-methylisoflavone 2′-O-β-d-glucopyranoside, 11), a sesquiterpene lactone (4,10-dihydroxy-8-methoxyguai-7(11)-en-8,12-olide, 5) and a new phenylpropanoid glycoside (boerhaavic acid, 15).     

Two new guaiane sesquiterpenes from Datura metel L. with anti-inflammatory activity

Chemical investigation of an acidic methanol extract of the whole plants of Datura metel resulted in the isolation of two new guainane sesquiterpenes, 1β,5α,7β-guaiane-4β,10α,11-triol (1) and 1α,5α,7α-11-guaiene-2α,3β,4α,10α,13-pentaol (2), along with eight known compounds: pterodontriol B (3), disciferitriol (4), scopolamine (5), kaempferol 3-O-β-d-glucosyl(1 → 2)-β-d-galactoside 7-O-β-d-glucoside (6), kaempferol 3-O-β-glucopyranosyl(1 → 2)-β-glucopyranoside-7-O-α-rhamnopyranoside (7), pinoresinol 4′′-O-β-d-glucopyranoside (8), (7R,8S,7′S,8′R)-4,9,4′,7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxy-lignan-4-O-β-d-glucopyranoside (9), and (7S,8R,7′S,8′S)-4,9,4′,7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxylignan-4-O-β-d-glucopyranoside (10). Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR and MS spectra. Compounds 2-4 and 6-10 were shown to have modest anti-inflammatory effects through inhibition of NO production in LPS-stimulated BV cells.     

Two new dihydrobenzofuran-type neolignans from Breynia fruticosa

(7S,8R,7′S)-9,7′,9′-Trihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (1) and (7S,8R,7′S)-9,9′-dihydroxy-3,4-methylenedioxy-3′,7′-dimethoxy [7-O-4′,8-5′] neolignan (2), two new natural dihydrobenzofuran-type neolignans, along with 9,9′-dihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (3) and (-)-machicendiol (4), were isolated from the whole plants of Breynia fruticosa. The structures of 1 and 2, including the absolute configurations, were determined by spectroscopic methods and circular dichroism (CD) techniques. The absolute configuration of 4 was confirmed by calculations of the OR spectrum, together with OR and ECD spectra of its p-bromobenzoate ester (4a).     

Platachromone A–D: Cytotoxic 2-styrylchromones from the bark of Platanus × acerifolia (Aiton) Willd.

Four novel 2-styrylchromones, 4′,5,7-trihydroxy-6-isopentene-2-styrylchromone (1), 4′,5,7-trihydroxy-8-isopentene-2-styrylchromone (2), 4′,5,7-trihydroxy-6-(2-hydroxy-3-methylbut-3-enyl)-2-styrylchromone (3) and 4′,5,7-trihydroxy-8-(2-hydroxy-3-methylbut-3-enyl)-2-styrylchromone (4), were isolated from shed bark of Platanus × acerifolia (Aiton) Willd., as well as four known compounds, 4′,5,7-trihydroxy-2-styrylchromone (5), scutellarein (6), 4′,5,7-trihydroxy-6-prenylflavone (7), and 4′,5,7-trihydroxy-8-prenylflavone (8). The structures of compounds 1–4 were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D and 2D NMR (¹H–¹H COSY, HSQC and HMBC). The cytotoxicity of the compounds 1–8 was evaluated in four human carcinoma cell lines, including HepG2, SMMC-7721, MDA-MB-231, and KB. Compounds 1–4 exhibited significantly cytotoxic activity toward HepG2 and KB cells, with IC₅₀ values ranging from 3.0 to 9.7 μM.     

Three new flavonoids from the leaves of oriental tobacco and their cytotoxicity

Three new flavonoids, 6,7-dimethoxy-4′-hydroxy-8-formylflavon (1), 8-formyl-4′,6,7-trimethoxyflavon (2), 4′,7-dihydroxy-8-formyl-6-methoxyflavon (3), together with fifteen known flavonoids (4–18) were isolated from the leaves of oriental tobacco (a variety of Nicotiana tabacum L). Their structures were determined by means of HRESIMS, extensive 1D and 2D NMR spectroscopic studies and chemical evidences. The cytotoxicity against five human tumor (NB4, A549, SHSY5Y, PC3, and MCF7) cell lines of compounds 1–3 were also evaluated. The results showed that compounds 1 and 3 showed high cytotoxicity against PC3 and A549 cell lines with IC₅₀ values of 2.6 and 1.6 μM, respectively.     

Ulmosides A and B: Flavonoid 6-C-glycosides from Ulmus wallichiana,stimulating osteoblast differentiation assessed by alkaline phosphatase

Chemical investigation of Ulmus wallichiana stem bark resulted in isolation and identification of three new compounds (2S,3S)-(+)-3′,4′,5,7-tetrahydroxydihydroflavonol-6-C-β-d-glucopyranoside (1), (2S,3S)-(+)-4′,5,7-trihydroxydihydroflavonol-6-C-β-d-glucopyranoside (3) and 3-C-β-d-glucopyranoside-2,4,6-trihydroxymethylbenzoate (8), together with five known flavonoid-6-C-glucosides (2, 4–7). Their structures were elucidated using 1D and 2D NMR spectroscopic analysis. The absolute stereochemistry in compounds 1 and 3 were established with the help of CD data analysis and comparison with the literature data analysis. All the isolated compounds (1–8) were assessed for promoting the osteoblast differentiation using primary culture of rat osteoblast as an in vitro system. Compounds 1–3 and 5 significantly increased osteoblast differentiation as assessed by alkaline phosphatase activity.