A new sacculatane diterpenoid and a new oplopanone sesquiterpenoid from Porella perrottetiana (Mont.) Trevis. collected in Sapa, Vietnam.

From the n-hexane extract of the liverwort Porella perrottetiana collected in Sapa (North Vietnam), a new sacculatane diterpenoid (perrottetianal E (1)) and a new oplopanone sesquiterpenoid ((+)-oplopanone C (2)), along with two known sesquiterpenes (3 and 4), and two known phaeophytins (5 and 6) have been isolated. Their structures were elucidated based on the analysis of NMR spectroscopic data, in combination with HR-ESIMS and the reported data. Compounds 1-4 were evaluated for their cytotoxic activities against three cancer cell lines: KB (human carcinoma in the mouth), HepG2 (human hepatocellular carcinoma), and A549 (human lung carcinoma).

Anti-Dengue Screening on Several Vietnamese Medicinal Plants: Experimental Evidences and Computational Analyses.

Worldwide, medicinal plants have been known for economic and geographical advantages, thus possibly holding potentiality against dengue hemorrhagic fever. The methanol/water extracts from different parts of fourteen Vietnam-based plant species were subjected for experimental screening on anti-dengue activity using baby hamster kidney cells (BHK21) and plaque reduction neutralisation test (PRNT). Firstly, the methanol/water extracts were tested against serotype dengue virus DENV-1. Seven out from nineteen extracts show the PRNT50 values less than 31.25 µg/mL. Four of the above extracts namely from Euphorbia hirta, Cordyline terminalis, Carica papaya, and Elaeagnus latifolia were chosen for testing against the serotype DENV-2. All of them exhibit good activity with the PRNT50 values less than 31.25 µg/ml, which were further fractionated to obtain hexane, ethyl acetate and butanol fractions. Anti-dengue virus activity of the fractions against four serotypes DENV-1, -2, -3 and -4 was evaluated. As results, the ethyl acetate fraction of Elaeagnus latifolia is highly active against all four serotype viruses. The structural formulae of its nine constituents were input for molecular docking simulation. The docking-based order for static inhibitability is 6-3L6P>7-3L6P>9-3L6P>2-3L6P>3-3L6P≈5-3L6P>9-3L6P>1-3L6P>8-3L6P; QSARIS-based analysis reveals the biocompatibility of the most promising ligands (4-7); ADMET-based analysis expects their pharmacological suitability. Exceptional finding on 2-3LKW hydrophilic interaction at Lys43 (with the associated Gibbs free energy of -10.3 kcal mol-1 ) raises an open explanation for inhibitory effects. The results encourage further investigations for more in-depth mechanisms and drug development, such as in vitro enzyme assays or in vitro clinical trials with natural substances from E. latifolia.

Chevalierinol A and B, two new neolignan sesquiterpenoids from Magnolia chevalieri.

Two new neolignan sesquiterpenoids, chevalierinol A (1) and chevalierinol B (2), were isolated from the ethyl acetate extract of Magnolia chevalieri leaves, together with twelve known compounds (3-14). Their structures were elucidated by analysis of spectroscopic data including 1D, 2D and mass spectra and compared with the reported data. Compounds 1, 3, 4, 6, 7, 10 were evaluated for their inhibitory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophage cells.

Cell Growth Inhibition of Saponin XII from Dipsacus japonicus Miq. on Acute Myeloid Leukemia Cells.

In previous studies, we isolated the known compound saponin XII from the roots of Dipsacus japonicus Miq. Here, we show that this compound reduced the number of acute myeloid leukemia OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses demonstrated that the reported activity was associated with a significant increase of apoptosis and of cells in the G0/G1 phase of the cell cycle, with a decrease of cells in the S and G2/M phases. Thus, the inhibition of cell growth in OCI-AML3 cells was due to antiproliferative and pro-apoptotic effects. Interestingly, the bioactivity of saponin XII exerted its effect at a concentration as low as 1 µg/mL.

Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines.

Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 µg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 µg/mL) and decreased the percentage of cells in S (50 µg/mL) and G2/M (50 and 25 µg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.

Artocarpus tonkinensis Protects Mice Against Collagen-Induced Arthritis and Decreases Th17 Cell Function.

Artocarpus tonkinensis (Moraceae) is a tree that grows in north Vietnam whose leaf decoction is used as a traditional remedy by the Hmong ethnic group to treat arthritis and backache. Our study evaluated the decoction's efficacy and mechanism of action in DBA/1J mice with collagen-induced arthritis (CIA). Mice treated with the decoction (At) either from the first collagen immunization or after CIA development experienced significantly less joint edema and inflammatory infiltration, whereas CIA-induced cartilage damage could only be prevented by early At treatment. Autoimmune gene expression profiles showed that Th17 cell-associated chemokine CCL20 and cytokines IL-6, IL-17, and IL-22 were strongly downregulated by At. Reduced expression of IL-2, IL-17, IL-22, and FasL in lymph node cells from At-treated mice was further confirmed by real-time PCR. The decoction also inhibited polarization of Th17 cells from CD4+ splenic T cells according to levels of IL-17 and RORC, a Th17 cell-specific transcription factor. Chromatographic analysis identified At's major component as maesopsin-ß-D-glucoside, which could inhibit in vitro differentiation of Th17 cells. The decoction significantly alleviated the signs and symptoms of CIA and inhibited the development and function of Th17 cells, highlighting its potent anti-inflammatory activity.

Two new prenylated isoflavones from Maclura cochinchinensis collected in Hoa Binh province Vietnam.

Two new prenylisoflavones, 3',4',5-trihydroxy-8-prenyl-dihydrofuran[2″,3″:7,6]isoflavone (1) and 4',5-dihydroxy-8-prenyl-dihydrofuran[2″,3″:7,6]isoflavone (2), along with five known prenylisoflavones (3-7), benzylalcohol-4-O-ß-d-glucoside (8) and two cinnamic acid esters (9, 10) were isolated from the leaves of Maclura cochinchinensis (Cudrania cochinchinensis). Their structures were elucidated by analysis of NMR (1H-, 13C-NMR, HSQC, HMBC), MS spectra and comparison with the published data. Compounds 4-10 were the first time isolated from this species. Prenylisoflavones 1-4 and 6-7 were evaluated for their in vitro cytotoxic activity on KB and HepG2 cancer cell lines. Compound 4 showed cytotoxic activity against both cancer cell lines with IC50 values of 26.99 and 19.95 µM, respectively. The other compounds were considered as inactive.

Chemical constituents of Oldenlandia pinifolia and their antiproliferative activities.

This study describes the chemical constituents of Oldenlandia pinifolia (Wall. Ex G. Don) Kuntze (synonym Hedyotis pinifolia Wall. Ex G. Don) and discusses their anti-proliferative activities. Thirteen compounds were isolated from the n-hexane, ethyl acetate and n-butanol extracts of whole plants O. pinifolia by chromatography method. Their structures were elucidated using MS and NMR analysis and compared with reported data. They are three anthraquinones, a carotenoid, two triterpenes, four iridoid glycosides and three flavonoid glycosides. Among them, 2-methyl-1,4,6-trihydroxy-anthraquinone is a new one, and three compounds were found for the first time in this genus. MTT assay resulted that the n-butanol extract and four isolated compounds inhibited the proliferation of chronic myelogenous leukaemia cells. The results from Hoechst 33343 staining and caspase 3-inducing exhibited that those four tested compounds induced apoptosis and activated caspase 3 (p < 0.05). One of them, isorhamnetin-3-O-ß-rutinoside showed the most activity with IC50 value of 394.68 ± 25.12 µM.

Chemical constituents from the leaves of Pinus dalatensis Ferré.

A phytochemical study of n-hexane and ethyl acetate extracts of Pinus dalatensis Ferré leaves led to the isolation of 11 compounds, including one caryolane sesquiterpenoid (1), five labdane diterpenoids (2, 3, 4, 5, 6), one serratane triterpenoid (7), one diacylated flavonoid glucoside (8), one stilbenoid (9) and two sterols (10, 11). The structural characterisation of the isolated compounds was elucidated by spectroscopic data and comparison with the literature report on the chemical constituents from Pinus dalatensis Ferré. Futhermore, three compounds 1, 4 and 6 were obtained for the first time from the genus Pinus. Besides, compounds (2, 3, 5, 8, 9) were also subjected to cytotoxicity effect on SK-LU-1, MCF-7 and Hep-G2 cell lines, but only compound 9 expressed activities with IC50 values of 141.22, 127.81 and 166.84 µM, respectively.

Efficient synthesis of thieno[3,2-b:4,5-b']diindoles and benzothieno[3,2-b]indoles by Pd-catalyzed site-selective C-C and C-N coupling reactions.

Heteroacenes (thieno[3,2-b:4,5-b']diindoles and benzothieno[3,2-b]indoles) were efficiently synthesized from tetrabromothiophene and 2,3-dibromobenzothiophene in two steps, respectively. In the first step, a site-selective Pd-catalyzed C-C coupling is carried out, followed by a two-fold C-N coupling with aromatic and aliphatic amines.

Cytotoxic and antimicrobial aporphine alkaloids from Fissistigma poilanei (Annonaceae) collected in Vietnam.

Two new aporphine alkaloids: 8-hydroxy-9-methoxy-1,2-methylenedioxyaporphine (1) and 8-hydroxy-3,9-dimethoxy-1,2-methylenedioxyaporphine (2) were isolated from the ethyl acetate extract of Fissistigma poilanei along with five known compounds: oxocrebanine (3), kuafumine (4), (2R,3R)-3',4',5,7-tetrahydroxydihydroflavonol-3-O-α-L-rhamnopyranoside (5), (+)-catechin 3-O-α-L-rhamnopyranoside (6) and quercetine 3,7-dimethoxy-3'-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranoside (7). These two new aporphine alkaloids exhibited a moderate cytotoxic activity against four human cancer cell lines (KB, Hep-G2, MCF-7, LU) as well as antimicrobial activity against Lactobacillus fermentum, Enterococcus faecium, Staphylococcus aureus and Bacillus subtillis.

A new dimeric carbazole alkaloid from Glycosmis stenocarpa roots.

A new dimeric pyranocarbazole alkaloid, bisisomahanine (1), was isolated from the roots of Glycosmis stenocarpa (DRAKE) TAN., along with two known monomeric carbazole alkaloids, murrayafoline-A (2) and murrayanine (3). The planar structure of bisisomahanine was determined to be 9,9''-dihydroxy-3,3'',8,8''-tetramethyl-3,3''-bis-(4-methyl-3-pentenyl)-3,3'',11,11''-tetrahydro-10,10''-(bipyrano[3,2-a]carbazole) from the combination of spectroscopic and chemical evidence. Bisisomahanine is the first dimeric prenylated pyranocarbazole alkaloid with a 1,1' type of linkage; the NMR and CD spectroscopic data indicated it to be a mixture of diastereomers having a dominant configuration at the axis of chirality. (1)H- and (13)C-NMR assignments of murrayafoline-A were made on the basis of 2D-experiments.

Homogentisic acid derivatives from Miliusa balansae.

The new homogentisic acid derivatives miliusol (1b) and miliusolide (2) from Miliusa balansae were isolated and structurally determined by spectroscopic means. The relative configurations of the new 1b and its known acetate 1a were established. Furthermore, the symmetric ether bis(2-hydroxyphenyl)methyl ether 3, which was isolated for the first time from a natural source, the known flavonoids pachypodol and chrysosplenol C, and sodium benzoate were identified.

Apotirucallane and Tirucallane triterpenoids from Luvunga sarmentosa.

The leaves of Luvunga sarmentosa yielded two new apotirucallane triterpenoids, 3-epi-skimmiarepin A (1) and 21,23-epoxy-7alpha,21-dihydroxyapotirucalla-14,24-dien-3-one (2), and a new tirucallane triterpene, 3-epi-flindissol (3). Because of a hemiacetal functionality at C-21, all compounds occurred as mixtures of 21-epimers. 3-epi-Skimmiarepin A (1) and 3-epi-flindissol (3) were oxidized to the corresponding gamma-lactones. The structures have been elucidated on the basis of mass and NMR spectroscopic methods.