Bioactivities of ß-mangostin and its new glycoside derivatives synthesized by enzymatic reactions.

Beta-mangostin is a xanthone commonly found in the genus Garcinia. Unlike α-mangostin, to date, there have only been a few studies on the biological activity and derivatization of ß-mangostin. In this study, two novel glycosylated derivatives of ß-mangostin were successfully synthesized via a one-pot enzymatic reaction. These derivatives were characterized as ß-mangostin 6-O-ß-d-glucopyranoside and ß-mangostin 6-O-ß-d-2-deoxyglucopyranoside by TOF ESI/MS and 1H and 13C NMR analyses. Beta-mangostin showed cytotoxicity against KB, MCF7, A549 and HepG2 cancer cell lines, with IC50 values ranging from 15.42 to 21.13 µM. The acetylcholinesterase and α-glucosidase inhibitory activities of ß-mangostin were determined with IC50 values of 2.17 and 27.61 µM, respectively. A strong anti-microbial activity of ß-mangostin against Gram-positive strains (Bacillus subtilis, Lactobacillus fermentum and Staphylococcus aureus) was observed, with IC50 values of 0.16, 0.18 and 1.24 µg ml-1, respectively. Beta-mangostin showed weaker activity against Gram-negative strains (Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa) as well as Candida albicans fungus, with IC50 and MIC values greater than the tested concentration (greater than 32 µg ml-1). The new derivatives of ß-mangostin showed weaker activities than those of ß-mangostin, demonstrating the important role of the hydroxyl group at C-6 of ß-mangostin in its bioactivity.

Desmodinosides A-E: New Flavonoid C-glycosides from Desmodium heterocarpon var. stigosum with hepatoprotective and antifungal activity.

Five new flavonoid C-glycosides named desmodinosides A-E (1-5) and one known compound, apigenin 6-C-ß-d-xylopyranosyl-2''-O-ß-D-glucopyranoside (6) have been isolated from the methanol extract of the aerial parts of Desmodium heterocarpon var. stigosum. These compounds were determined by 1D and 2D-NMR and HR-MS spectroscopies. The methanol extract of this plant, in particular, demonstrated hepatoprotection and antifungal inhibition. This extract has a remarkable hepatoprotection and activity-dose response with an EC50 of 43.07 µg/mL. The hepatoprotective effect on human liver hepatoma cells (HepG2) of the isolated flavonoid C-glycosides 1-6 was observed. Desmodinosides A-C (1-3) were found to exhibit moderate hepatoprotective activity on HepG2 cells. Of these, compound 2 showed the best hepatoprotective activity with an EC50 value of 74.12 µg/mL. While compounds 1 and 3 displayed EC50 values of 271.21 and 211.99 µg/mL, respectively. Quercetin, a positive control, also caused an EC50 value of 36.42 µg/mL. In addition to having hepatoprotective effect, the methanol extract had an inhibitory effect on the growth of oomycete; it inhibited Phytophthora infestans with IC50 of 13.3 µg/mL and IC90 of 78.7 µg/mL. The oomycete inhibition was directly attributed to compounds 5 and 6, which significantly inhibited P. infestans with IC50 values of 27.4 and 24.7 µg/mL, respectively. Both 5 and 6 and methanol extract were active against P. infestanse in a dose-dependent manner. Our study demonstrated for the first time the new flavonoid C-glycosides from D. heterocarpon var. stigosum and their novel pharmacological properties. The study findings also suggest the plant extract and its metabolites could be used as a new botanical source of bioactive compounds.

Characterization of thymol derivatives from Eupatorium fortunei Turcz. aerial parts.

From the aerial parts of Eupatorium fortunei, four thymol derivatives (1-4) were isolated and structurally elucidated by NMR and mass spectroscopic methods. Of which, a new dimeric thymol derivative (1) was characterized and its absolute configuration was established by electronic circular dichroism quantum method. In addition, the 1D and 2D NMR as well as HR-ESI mass spectral data of 2 were provided for the first time. Compounds 2-4 were evaluated for their inhibitory activity against α-glucosidase and acetylcholinesterase enzymes. All tested compounds showed weak inhibition at the concentration range of 1-256 µg/mL in both enzymatic assays.

New cycloartane coronalyl acetate and other terpenoids with anti-inflammatory activity from the leaves of Vietnamese Gardenia philastrei.

Phytochemical study on the methanolic extract of the leaves of Vietnamese plant Gardenia philastrei Pierre ex Pit. has led to the isolation of a new cycloartane coronalyl acetate (1) together with six known ones, coronlolide methyl ester (2), sootepin D (3), coronalolide (4), coronalolic acid (5), sootepin G (6) and 23-deoxojessic acid (7). Their structures were elucidated by a combination of 2 D NMR and HR-ESI-MS spectroscopies. These compounds (1-7) were tested for their anti-inflammatory activity. The result showed that six compounds (1-6) inhibit LPS-induced nitric oxide production in RAW264.7 macrophages with their IC50 values ranging from 3.76 - 75.47 µg/mL. This is the first report on the chemical constituents and anti-inflammatory activity of the G. philastrei.

Endertiins A-B, two lanostane triterpenoids from the fruit bodies of the mushoom Humphreya endertii.

Two new lanostane triterpnenoids named endertiins A and B (1 and 2) together with two known compounds as ganodecalone A (3) and ergosterol (4) have been successfully isolated from the cultivated fruit bodies of the mushroom Humphreya endertii Stey (Ganodermataceae). Their structures were elucidated by a combination of HR-MS and 2 D NMR spectroscopic analyses. In addition, endertiins A and B (1 and 2) were evaluated their cytotoxicity against two cancer cell lines, MCF7 (human breast carcinoma) and LU (human lung carcinoma). The result showed that endertiin A (1) could inhibit the growth of MCF-7 cells with its IC50 value of 71.16 ± 6.25 µg/ml.

Triterpenoids and steroids from the fruiting bodies of Hexagonia tenuis and their cytotoxicity.

One new triterpenoid, hexagonin F (1) was characterized from the fruiting bodies of Hexagonia tenuis with the assistance of spectroscopic and spectrometric analytical methods. In addition, two triterpenoids and two steroids were also identified by comparison of their physical and spectroscopic data with those reported. The purified compounds were examined for their cytotoxicity against five tumor cell lines, however, only weak cytotoxicity was demonstrated.

Cytotoxic constituents from Helicteres hirsuta collected in Vietnam.

Phytochemical study on the extract of Vietnamese medicinal plant Helicteres hirsuta Lour. has led to the isolation and structural elucidation of twelve secondary metabolites, 3-O-trans-caffeoylbetulinic acid (1), 3ß-benzoylbetulinic acid (2), betulinic acid methyl ester (3), betulinic acid (4), lupeol (5), 4-hydroxybenzoic acid (6), 3,4-dihydroxybenzoic acid methyl ester (7), 4-hydroxy-3,5-dimethoxybenzoic acid (8), 5,8-dihydroxy-7,4'-dimethoxyflavone (9), isoscutellarein 4'-methyl ether 8-O-ß-D-glucopyranoside (10), methyl caffeate (11) and stigmasterol (12). Especially, compound 2 was reported as a new natural product. Their structures were elucidated by a combination of 2D NMR and ESI-FT-ICR-MS spectroscopies. Furthermore, eight compounds were tested for their cytotoxicity against five cancer cell lines (Hela, HepG2, SK-LU-1, AGS and SK-MEL-2). The results showed that compounds (1, 3-5, 9) have moderate activities. This is the first study on the chemical constituents and their cytotoxicity of the Vietnamese Helicteres hirsuta L.

Acemosin- a cytotoxic 20-norsteroid from Asparagus racemosus.

A novel cytotoxic 20-norsteroid with twenty-six carbon atoms named acemosin (1) was isolated and structural characterized together with two known compounds, asparacosin A (2) and stigmasterol (3) from the roots of Asparagus racemosus. Their structures were elucidated by a combination of 2D NMR, HR-MS and X-ray crystallographic analyses. Acemosin (1) possesses an unprecedented carbon skeleton, where the methyl group at C-20 is absent. Acemosin shows moderate cytotoxicity against HepG2 cancer cell line with its IC50 value of 87.3 µg/mL.

Balanochalcone, a new chalcone from Balanophora laxiflora Hemsl.

A new chalcone named as balanochalcone (1) together with eight known compounds, methyl caffeate (2), ß-hydroxydihydrochalcone (3), methyl gallate (4), dimethyl-6,9,10-trihydroxybenzo[kl]xanthene-1,2-dicarboxylate (5), p-coumaric acid (6), quercetin (7), scopoletin (8) and pinoresinol (9) have been isolated from the ethyl acetate extract of Vietnamese Balanophora laxiflora Hemsl. Their structures were characterised by IR, UV, HR-ESI-MS, 1D and 2D NMR and CD spectroscopies. Compounds 2 and 5 showed moderate cytotoxicity against four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma). In addition, compounds 1 and 5 showed moderate antioxidant activity.

Pyrofomins A-D, polyoxygenated sesquiterpenoids from Pyrofomes demidoffii.

Pyrofomins A-D, four polyoxygenated sesquiterpenoids have been isolated from the methanolic extract of the fruit bodies of Pyrofomes demidoffii. Their structures are elucidated by IR, HR-FTICR-MS, and 2D NMR spectroscopy. Furthermore, the cedrane carbon skeleton of pyrofomin A (1) is confirmed by X-ray crystallographic analysis. The sesquiterpenoids 1-4 show neither cytotoxicity against KB cells nor antimicrobial activity.

Anti-inflammatory activity of methyl ferulate isolated from Stemona tuberosa Lour.

OBJECTIVE: To evaluate the anti-inflammatory activity of methyl ferulate (MF) isolated from the roots of Stemona tuberosa (S. tuberosa) Lour (Stemonaceae) in lipopolysaccharide activated macrophage cells. METHODS: Methanol extracts of a root powder of S. tuberosa were prepared for isolation of a potential anti-inflammatory agent using ultrasound extraction combined with repeated chromatography on silica gel. After the quantitative analyses, anti-inflammatory activity of the isolated compound was evaluated by measurement of cytokine release, NO generation, expression of cyclooxygenase-2 and phosphorylation of mitogen activated protein kinases including p38 and c-Jun NH2-terminal kinase using quantitative kits and Western blotting with specific antibodies. RESULTS: The isolation process yielded a potential anti-inflammatory compound with a purity level of 99% determined by high performance liquid chromatography. The compound was identified as MF by using nuclear magnetic resonance. MF strongly inhibited the release of pro-inflammatory cytokines from macrophages, including IL-6, TNFα, IFNγ, yet it did not affect the anti-inflammatory cytokine IL-10. Phosphorylation of p38 and c-Jun NH2-terminal kinase were clearly reduced in MF-treated macrophages stimulated with lipopolysaccharide. cyclooxygenase-2 expression and NO generation by macrophages were also suppressed when the cells were treated with MF. CONCLUSIONS: The data suggested that MF is a possible inhibitor of the mitogen activated phosphor kinase pathway and could be a potential anti-inflammatory agent isolated for the first time in medicinal plant S. tuberosa.

Cytotoxic constituents from the Vietnamese fungus Xylaria schweinitzii.

Two new fungal pigments named schweinitzins A and B (1-2), together with (S)-torosachrysone-8-O-methyl ether (3) and emodin-6,8-di-O-methyl ether (4) have been isolated from the methanolic extract of the fruit bodies of Xylaria schweinitzii (Xylariaceae) collected in Cuc Phuong national park, Ninh Binh province, Vietnam, by silica gel column chromatography and preparative HPLC. Their structures were elucidated by spectroscopic analysis such as IR, UV-Vis, 2D NMR and FT-ICR-MS. In addition, two compounds (1 and 3) showed strong cytotoxicity against all four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-I (human lung carcinoma) and HepG2 (hepatocellular carcinoma).

Stemofurans X-Y from the roots of Stemona species from Laos.

Two new phenylbenzofuran-type stilbenoids named stemofurans X and Y (1, 2) were isolated from the roots of Stemona pierrei and S. tuberosa, respectively, together with ten known compounds. These compounds were stemanthrenes B-C (3, 4), (+)-syringaresinol (5), maistemonine (6), isomaistemonine (7) and sesamin (8) from S. pierrei, and stemophenanthrenes A-C (9-11) and isopinosylvin A (12) from S. tuberosa. Stemofurans X-Y (1, 2) showed moderate cytotoxicity against the four cancer cell lines KB (human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma), and Hep-G2 (hepatocellular carcinoma).

Three new phenanthrenes, a new stilbenoid isolated from the roots of Stemona tuberosa Lour. and their cytotoxicity.

Three new phenanthrenes, stemophenanthrenes A-C (1-3), along with one new stilbenoid, isopinosylvin A (4) and a known compound methyl ferulate (5), were isolated and identified from the roots of Stemona tuberosa Lour. plants, collected in Attapu province (Laos). Their structures were elucidated by spectroscopic analysis (FT-ICR-MS, IR, UV, 1D and 2D NMR). These compounds show moderate cytotoxic activity against four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).

Cattienoids A-C, three novel steroids from the mushroom Tomophagus cattienensis.

Three novel steroids (1-3), named cattienoids A-C together with schisanlactone A (4), were isolated from fruiting bodies of Tomophagus cattienensis (Ganodermataceae)-a new mushroom recently collected from Cattien National Park, in Viet Nam. They possess an unusual seven membered lactone ring, derived from lanostane-type triterpenoids. Their structures were determined by spectroscopic methods. In addition, compounds 2 and 4 showed cytotoxicity against KB (a human epidermal carcinoma) cells with their IC50 values of 91.2 and 63.3 µM, respectively. These compounds have neither antimicrobial activity nor inhibition of the tyrosinase.

Cytotoxic constituents from the fungus Daldinia concentrica (Xylariaceae).

Phytochemical study on the methanol extract of the fruit bodies of Vietnamese fungus Daldinia concentrica has led to the isolation and structural elucidation of three cytotoxic constituents, 6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin (1), (22R)-hydroxylanosta-7,9(11),24-trien-3-one (2) and ergosterol (3). Their structures were elucidated by 2D-NMR and FT-ICR-MS. All the three compounds showed moderate cytotoxicity against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma). In addition, the isocoumarin (1) inhibited the growth of Staphylococcus aureus with the IC50 value of 87.81 µg mL(-1).

Main constituents from the seeds of Vietnamese Cnidium monnieri and cytotoxic activity.

From the ethyl acetate extract of the seeds of Vietnamese Cnidium monnieri L., three coumarins, osthole (1), xanthotoxin (2), imperatorin (3) and a sterol, daucosterol (4) have been purified. Their structures were elucidated by spectroscopic analysis. Furthermore, 8-(3-hidroxy-3-methylbutyl)-7-methoxycoumarin (5) was synthesised from osthole (1) with a good yield (80%). In addition, compound 1 and its synthesis product (5) show moderate and non-selective cytotoxic activities against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).

Ampullosine, a new isoquinoline alkaloid from Sepedonium ampullosporum (Ascomycetes).

A new isoquinoline alkaloid, ampullosine (3-methyl-isoquinoline-6-carboxylic acid, 1), was isolated from Sepedonium ampullosporum and characterized by spectroscopic analysis and chemical reactions. This compound is responsible for the deep yellow color of the culture fluid of this species. Moreover, the known compounds sepedonin (2) and anhydrosepedonin (3) were detected. Twelve strains belonging to eight species of Sepedonium have been screened for these three metabolites by LC/ESI-SRM (selected reaction monitoring). Ampullosine (1) could be detected in almost all species in Sepedonium, but not in the phylogenetically more distant species S. brunneum and S. tulasneanum. Anhydrosepedonin (3) showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum.

Chemical constituents of the Vietnamese liverwort Porella densifolia.

From the ether extract of Porella densifolia, the first liverwort collected and chemically investigated in Vietnam, a kaurane diterpenoid, ent-kauren-15-one (1) and two sesquiterpene norpinguisone (2) and norpinguisone methyl ester (3) have been purified. Their structures were elucidated by spectroscopic analysis. In addition, an X-ray crystal structure of norpinguisone was obtained, allowing to determine its stereochemistry. Furthermore, the inhibitory activity of nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) of compounds 1-3 was examined with their IC(50) values of 69.4, 45.5 and 1.68 microM, respectively.

Alkaloids from the mushroom Pseudobaeospora pyrifera, pyriferines A-C.

Three novel alkaloids (1-3), named pyriferines A-C, were isolated from fruiting bodies of Pseudobaeospora pyrifera. They possess an unusual eight-membered N/O-acetal ring, derived from L-glutamic acid, that is connected to an enolized 1,3-diketo moiety. The structures were determined by spectroscopic methods, and the absolute configuration of the glutamic acid moiety was established using GC-MS after Mosher-type derivatization.