Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam.

Bioactive-guided phytochemical investigation of Euphorbia antiquorum L. growing in Vietnam led to the isolation of five ent-atisanes, one seco-ent-atisane, and one lathyrane (ingol-type). The structures were elucidated as ent-1α,3α,16ß,17-tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylate (2), ent-atisane-3-oxo-16ß,17-acetonide (3), ent-3α-acetoxy-16ß,17-dihydroxyatisane (4), ent-16ß,17-dihydroxyatisane-3-one (5), calliterpenone (6), and ingol 12-acetate (7). Their chemical structures were unambiguously determined by analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry, as well as by comparison with literature data. Among them, 1 is a new compound while 2 is an ethylated artifact of ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylic acid, a new compound. Isolates were evaluated for alpha-glucosidase inhibition. Compound 3 showed the most significant inhibitory activity against alpha-glucosidase with an IC50 value of 69.62 µM. Further study on mechanism underlying yeast alpha-glucosidase inhibition indicated that 3 could retard the enzyme function by noncompetitive.

Flavones from Combretum quadrangulare Growing in Vietnam and Their Alpha-Glucosidase Inhibitory Activity.

Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.

Nervisides I-J: Unconventional Side-Chain-Bearing Cycloartane Glycosides from Nervilia concolor.

Two new cycloartane glycosides, nervisides I-J, were isolated from Nervilia concolor whole plants. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data. These cycloartanes comprised a stereogenic center at C-24, the R configuration of which was assigned based on DFT-NMR calculations and the subsequent DP4 probability score. These compounds were tested for cytotoxicity against K562 and MCF-7 tumor cell lines, revealing mild cytotoxic activity.

A new sesquiterpene lactone from the leaves of Panax vietnamensis Ha et Grushv. (Vietnamese ginseng).

Panax vietnamensis (Vietnamese ginseng, Ngoc Linh ginseng) is an endemic Panax species of Vietnam. From the methanol extract of the leaves of Panax vietnamensis, five compounds (1-5) were isolated, including one new sesquiterpene lactone such as panaxolide (1) and four known compounds. The structures of the compounds (1-5) were elucidated by spectral techniques such as 1 D NMR (1H NMR, 13C NMR), 2 D NMR (COSY, HSQC, HMBC, NOESY) and mass spectrometry. The absolute configuration of 1 was determined based on the Cotton effects in the CD spectrum. All of the five compounds were screened for their in vitro growth inhibitory activities against cancerous cells (HepG2) and normal cells (fibroblast) using the SRB assay. Panaxolide (1) showed the highest potential for the growth inhibition of cancerous cells HepG2 with the IC50 values of 63.8 µM.

Parmosidone K, a new meta-depsidone from the lichen Parmotrema tsavoense.

Further phytochemical investigation on P. tsavoense led to one new meta-depsidone, parmosidone K together with one known compound, barbatic acid. Their structures were determined by 1D and 2D NMR analysis, high resolution mass spectroscopy, and comparison their NMR data with those reported in literatures. Parmosidone K was evaluated for α-glucosidase inhibition and revealed the powerful activity with IC50 value of 3.12 µM.

Nervione, a new benzofuran derivative from Nervilia concolor.

A new benzofuran derivative, nervione (1), was isolated from Nervilia concolor (Blume) Schltr. (Orchidaceae). Eight previously reported compounds were also isolated: 5,7-dimethoxyflavone (2), 3,5,7-trimethoxyflavone (3), 7-methoxyflavone (4), 3,7-dimethoxy-5-hydroxyflavone (5), tetramethylscutellarein (4',5,6,7-tetramethoxyflavone) (6), 5,7-dimethoxy-4'-hydroxyflavone (7), rhamnetin (8), and 5,7-dihydroxy-3',4'-dimethoxyflavone (9). The structures were elucidated by 1D, 2D NMR, and HRESIMS spectroscopy in addition to the literature. The relative configuration of 1 was defined using DP4+ probability while its absolute configuration was defined by comparison of the ECD spectrum of 1 with those of previously reported compounds. All isolated compounds were evaluated for alpha-glucosidase inhibition, revealing weak or no activity.[Formula: see text].

Cytotoxic activity and phytochemical composition of Stereospermum binhchauensis V.S. Dang leaves.

For the first time, the cytotoxic and phytochemical investigation of the leaves of Stereospermum binhchauensis V.S. Dang, a new species discovered in Viet Nam were finalized and led to purify nine compounds, including one furancoumarin (1), one chromone (3), two triterpenoids (2, 4), two flavonoids (5, 8), two flavanoids (6, 7) and one iridoid (9) using various chromatography methods. Their structures were verified by HR-ESI-MS, NMR experiments and compared with previous literatures. For the first time, compounds (5-8) were realized from the genus Stereospermum, while compounds (1, 2, 3, 4 & 9) were designated from the species S. binhchauensis. Furthermore, the furancoumarin, chromone and flavanoid classes were notified for the first time from the genus Stereospermum.

Polysciosides J and K, two new oleanane-type triterpenoid saponins from the leaves of Polyscias fruticosa (L.) harms. cultivating in An Giang Province, Viet Nam.

For the first time, the phytochemical constituents of the leaves of Polyscias fruticosa (L.) Harms. cultivating in An Giang Province, Viet Nam were investigated and led to purify two new oleanane-type triterpenoid saponins, named polyscioside J (1) and polyscioside K (2) together with two known saponins, ladyginoside A (3) and chikusetsusaponin IVa (4) using variously chromatographic methods. Saponin (4) was reported for the first time from this species. Their structures were verified by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with previous literatures.

Markhasphingolipid A, new phytosphingolipid from the leaves of Markhamia stipulata var. canaense V.S. Dang.

From the leaves of Markhamia stipulata var. canaense V.S. Dang, one new phytosphingolipid, named markhasphingolipid A (6) together with five known compounds, 4',7-O-dimethylapigenin (1), narigenin (2), tectoquinone (3), mollic acid (4), 1-hexadecanoyl-sn-glycerol (5) were classified by various chromatographic methods. Their structures were designated by IR, UV, HR-ESI-MS, HR-ESI-MS/MS and NMR experiments. All compounds were recognized for the first time from this species. The cytotoxicity of all n-hexane fractions and isolated compounds (5 & 6) against three human cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated by SRB assay. All n-hexane fractions expressed cytotoxic effect on three tested cancer cell lines (at the concentration of 100 µg/mL, percent of cytotoxicity ranged from 55.81% to 95.83%) as well as compound 5 (IC50 ranged from 48.51 to 63.30 µM) whereas fraction H.I and compound 6 did not show activity.[Formula: see text].

Markhacanasin C, cycloartane triterpenoid from the leaves of Markhamia stipulata var. canaense V.S. Dang.

One new cycloartane triterpenoid, named markhacanasin C (1), together with three known triterpenoids, oleanolic acid (2), ursolic acid (3) and 6ß,19α-dihydroxyursolic acid (4) were isolated by various chromatographic methods from the most cytotoxic fraction of the ethyl acetate extract of Markhamia stipulata var. canaense V.S. Dang leaves. Among them, 4 was reported for the first time from the genus Markhamia, while 2 and 3 were found for the first time from this species. Their structures were elucidated by IR, UV, HR-ESI-MS and NMR experiments. The cytotoxicity of isolated compounds (3 and 4) against three human cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated. At the concentration of 100 µg/mL, 3 exhibited significant cytotoxic activity (86.36 ± 3.69%).

Flavonoids with hepatoprotective activity from the leaves of Cleome viscosa L.

One new flavonol glycoside named visconoside C (1), together with seven known flavonol glycosides, quercetin 3-O-ß-d-glucopyranoside 7-O-α-l-rhamnopyranoside (2), quercetin 7-O-α-l-rhamnopyranoside (3), astragalin (4), kaempferol 3-O-(4-O-acetyl)-α-l-rhamnopyranoside (5), kaempferol 7-O-α-l-rhamnopyranoside (6), kaempferitrin (7) and kaempferol 3-O-ß-d-glucopyranoside 7-O-α-l-rhamnopyranoside (8) were isolated by various chromatography methods from the leaves of Cleome viscosa L. Their structures were elucidated by IR, UV, HR-ESI-MS and NMR (1D & 2D) experiments. The cytotoxicity and hepatoprotective activities using HepG2 human hepatoma cell line of 1 were measured by MTT assay. At the concentration of 25 µM and 50 µM, 1 showed cytotoxic activity against HepG2 cells (cell viability was decreased to 22.2 and 23.0%, respectively, compared with doxorubicin control), while at the concentration of 100 µM, 1 showed hepatoprotective activity against CCl4-induced hepatotoxicity on HepG2 cells (34.3%, compared with quercetin control).