Sulfated Naphthopyrones and Anthraquinones from the Vietnamese Crinoid Comanthus delicata.

Three new sulfated naphthopyrone derivatives namely delicapyrons F-H (1-3) and two new sulfated anthraquinone derivatives namely delicaquinons A (4) and B (5), together with 6-methoxycomaparvin-5-methylether-8-O-sodium sulfate (6), 6-methoxycomaparvin-8-O-sodium sulfate (7), comaparvin-8-O-sodium sulfate (8), and 3-propyl-1,6,8-trihydroxy-9,10-anthraquinone-6-O-sodium sulfate (9) were isolated from the Vietnamese crinoid Comanthus delicata. Their chemical structures were elucidated by extensive analysis of the one dimensional (1D) and 2D-NMR, high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra as well as calculation of optical rotation. In addition, significant cytotoxicity was observed for 6 against LNCaP (prostate cancer) cell line with IC50 value of 20.29 ± 2.43 µM, whereas moderate or weak cytotoxic effects were observed for 1-3 and 5-8 on SK-Mel-2 (melanoma) cell line and 7 and 8 against LNCaP cell line, with IC50 values ranging from 49.96 ± 1.74 to 76.92 ± 5.85 µM.

Cytotoxic constituents from Isotrema tadungense.

In our search for cytotoxic constituents from Vietnamese plants, the methanolic extract of Isotrema tadungense was found to exhibit significant cytotoxic effect. Subsequent phytochemical investigation of ethyl acetate fractions of this plant led to isolation of 11 compounds including one new arylbenzofuran rhamnoside namely aristolochiaside (1), two aristololactams (2 and 3), three lignanamides (4-6) and five phenolic amides (7-11). Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among the isolated compounds, aristolochiaside (1), aristolactam AIIIa (2) and N-trans-sinapoyltyramine (10) exhibited strong and selective cytotoxicity on the HeLa human cancer cell line with IC50 values of 7.59 ± 1.03, 8.51 ± 1.73 and 9.77 ± 1.25 µM, respectively.[Formula: see text].

Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.

Mallotusapelta(Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M.apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovariancancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 µM and IC50 values ranging from 1.62 to 10.42 µM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.

Diterpenoids and Flavonoids from Andrographis paniculata.

Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.

Dendrodoristerol, a cytotoxic C20 steroid from the Vietnamese nudibranch mollusk Dendrodoris fumata.

Using various chromatographic separations, four steroids including one new C20 steroid namely dendrodoristerol (1), were isolated from the Vietnamese nudibranch mollusk Dendrodoris fumata. The structure elucidation was confirmed by combination of spectroscopic experiments including 1D and 2D NMR, HR QTOF MS, and CD. Compound 1 was found to exhibit significant in vitro cytotoxic activity against six human cancer cell lines as HL-60, KB, LU-1, MCF-7, LNCaP, and HepG2. In addition, 1 induced HL-60 cancer cell death by apoptosis and necrosis.

Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 µM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Five New Pregnane Glycosides from Gymnema sylvestre and Their α-Glucosidase and α-Amylase Inhibitory Activities.

Gymnema sylvestre, a medicinal plant, has been used in Indian ayurvedic traditional medicine for the treatment of diabetes. Phytochemical investigation of Gymnema sylvestre led to the isolation of five new pregnane glycosides, gymsylosides A-E (1-5) and four known oleanane saponins, 3ß-O-ß-D-glucopyranosyl (1→6)-ß-D-glucopyranosyl oleanolic acid 28-O-ß-D-glucopyranosyl ester (6), gymnemoside-W1 (7), 3ß-O-ß-D-xylopyranosyl-(1→6)-ß-D- glucopyranosyl-(1→6)-ß-D-glucopyranosyl oleanolic acid 28-O-ß-D-glucopyranosyl ester (8), and alternoside XIX (9). Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Compounds 2-4 showed significant α-amylase inhibitory activity, with IC50 values ranging from 113.0 to 176.2 µM.

Cyclobutastellettolides A and B, C19 Norterpenoids from a Stelletta sp. Marine Sponge.

Two novel C19 terpenoids (1, 2) with an unprecedented carbon skeleton (A) were isolated from a Stelletta sp. sponge collected from Vietnamese waters. Their structures and absolute configurations were established by extensive NMR, MS, and ECD analyses together with quantum chemical modeling and biogenetic considerations. The probable pathways of biogenesis of 1 and 2 from isomalabaricane triterpenoids are discussed. Compounds 1 and 2 significantly increase the production of reactive oxygen species in murine peritoneal macrophages.

Anthraquinone and Butenolide Constituents from the Crinoid Capillaster multiradiatus.

Seven anthraquinones including two new compounds namely capillasterquinones A and B (1 and 2) and one new butenolide namely capillasterolide (8) were isolated and structurally elucidated from the crinoid Capillaster multiradiatus. The inhibitory effect of compounds 1-8 on lipopolysaccharide (LPS)-induced nitric oxide (NO) production as well as inhibition of 1 on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins in RAW264.7 cells were also evaluated. As the obtained results, capillasterquinone A (1) showed strong NO production inhibitory activity with an IC50 of 5.89±0.11 µM. In addition, compound 1 reduced the LPS-induced iNOS and COX-2 expressions in a dose-dependent manner.

Two new guaiane sesquiterpene lactones from the aerial parts of Artemisia vulgaris.

Two new guaiane sesquiterpene lactones, vulgarolides A and B (1 and 2), were isolated from Artemisia vulgaris aerial parts using various chromatographic separations. The structure elucidation was performed by combination of spectroscopic experiments including 1D and 2D NMR, HR ESI MS, and CD. Their in vitro cytotoxic activities against five human cancer cell lines were also evaluated using SRB method.

Two New Steroidal Monoglycosides, Anthenosides A1 and A2, and Revision of the Structure of Known Anthenoside A with Unusual Monosaccharide Residue from the Starfish Anthenea aspera.

Two new polyhydroxysteroidal glycosides, anthenosides A1 (1) and A2 (2), and one previously known steroidal glycoside anthenoside A (3) were isolated from extract of the tropical starfish Anthenea aspera. Structures of 1⁻3 were determined by analysis of the spectroscopic data as well as chemical transformations. As a result, the structure of anthenoside A has been revised and the structures of 1 and 2 were established. Glycosides 1⁻3 contain a 2-acetamido-2-deoxy-4-O-methyl-ß-d-glucopyranosyl residue, found in the starfish steroidal glycosides for the first time. All the isolated compounds slightly inhibited cell viability of human cancer T-47D cells and did not show cytotoxic effects against RPMI-7951 cells. Glycoside 1 slightly inhibited colony formation of human cancer RPMI-7951 cells by 16% while compound 2 decreased the number of colonies of T-47D cells by 40%.

Flavonoid glycosides from Barringtonia acutangula.

Using various chromatographic separation techniques, ten flavonoid glycosides, including six new compounds namely barringosides A-F (1-6), were isolated from a methanol extract of the Barringtonia acutangula leaves. The structure elucidation was confirmed by spectroscopic analyses, including 1D and 2D NMR, and HR ESI MS. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were also evaluated. Among the isolated compounds, quercetin 3-O-ß-d-(6-p-hydroxybenzoyl)galactopyranoside (9) showed significant effect with an IC50 of 20.00±1.68µM. This is the first report of these flavonoid glycosides from Barringtonia genus and their inhibition on LPS-induced NO production in RAW264.7 cells was reported here for the first time.

Sesquiterpene derivatives from marine sponge Smenospongia cerebriformis and their anti-inflammatory activity.

Using various chromatographic methods, five new sesquiterpene derivatives named smenohaimiens A-E (1-5) and five known, 19-hydroxy-polyfibrospongol B (6), ilimaquinone (7), dictyoceratin C (8), polyfibrospongol A (9), and polyfibrospongol B (10) were isolated from the marine sponge Smenospongia cerebriformis Duchassaing & Michelotti, 1864. Their structures were assigned by 1D, 2D NMR spectroscopic analysis, HR ESI MS, and calculations of the electron circular dichroism spectra. All compounds were evaluated for the inhibitory activity against NO production in lipopolysaccharide-stimulated in BV2 microglia cells. As the results, compound 7 significantly inhibited NO production with the IC50 value of 10.40±1.28µM. The remaining compounds showed moderate inhibitory NO production activities with IC50 values ranging from 24.37 to 30.43µM.

Triterpene saponins and megastigmane glucosides from Camellia bugiamapensis.

Two new triterpene saponins, camelliosides I and J (1 and 2), two new megastigmane glycosides, camellistigosides A and B (3 and 4), and two known megastigmane glycosides, icariside B1 (5) and (6S,9R)-roseoside (6), were isolated from a methanol extract of the Camellia bugiamapensis leaves using various chromatographic separation techniques. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, CD, 1D and 2D NMR. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were evaluated. This is the first report of the chemical constituents and biological activity of C. bugiamapensis.

Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens.

Using various chromatographic separation techniques, eight triterpene diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1-4), were isolated from a methanol extract of the Vietnamese sea cucumber S. horrens. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide A (5), and 3ß-O-[ß-d-xylopyranosyl-(1→2)-ß-d-xylopyranosyl]-23S-acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell lines, whereas significant effect was observed for stichorrenoside C (3) and stichoposide B (6).

Cytotoxic Steroids from the Vietnamese Soft Coral Sinularia leptoclados.

Fifteen steroids, including two new compounds, leptosteroid (1) and 5,6ß-epoxygorgosterol (2), were isolated and structurally elucidated from the Vietnamese soft coral Sinularia leptoclados. Their cytotoxic effect against a panel of eight human cancer cell lines was evaluated using sulforhodamine B (SRB) method. Significant cytotoxicity against hepatoma cancer (HepG2, IC50=21.13±0.70 µM) and colon adenocarcinoma (SW480, IC50=28.65±1.53 µM) cell lines were observed for 1 and against acute leukemia (HL-60, IC50=20.53±2.26 µM) and SW480 (IC50=26.61±1.59 µM) for ergost-5-en-3ß,7ß-diol (8). In addition, 3ß,7ß-dihydroxyergosta-5,24(28)-diene (13) showed significant cytotoxic activity on all tested cell lines with IC50 values ranging from 13.45±1.81 to 29.01±3.21 µM.

Cytotoxic Steroids from the Vietnamese Soft Coral Sinularia conferta.

Twelve steroids, including five new compounds 1-5, were isolated and structurally elucidated from a methanol extract of the Vietnamese soft coral Sinularia conferta. Their cytotoxic effects against three human cancer cell lines, lung carcinoma (A-549), cervical adenocarcinoma (HeLa), and pancreatic epithelioid carcinoma (PANC-1), were evaluated using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays. Among isolated compounds, 10 exhibited potent cytotoxic effects on all three tested cell lines with IC50 values of 3.64±0.18, 19.34±0.42, and 1.78±0.69 µM, respectively.

Steroid glycosides from the starfish Pentaceraster gracilis.

Using combined chromatographic separations, two new steroid glycosides namely pentacerosides A (1) and B (2), and four known compounds were isolated from the methanol extract of the starfish Pentaceraster gracilis. Their structures were determined on the basis of spectroscopic data (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, ROESY, and FT-ICR-MS) and by comparing obtained results to the literature values. Among the isolated compounds, only maculatoside (5) showed significant cytotoxic effect against Hep-G2 (IC50 = 16.75 ± 0.69 µM) and SK-Mel2 (IC50 = 19.44 ± 1.45 µM) cell lines and moderate effect on KB (IC50 = 36.53 ± 0.78 µM), LNCaP (IC50 = 39.75 ± 3.34 µM), and MCF7 (IC50 = 47.34 ± 7.01 µM) cell lines.

Prenylated isoflavones from Cudrania tricuspidata inhibit NO production in RAW 264.7 macrophages and suppress HL-60 cells proliferation.

Inhibitory effects of NO production in RAW 264.7 macrophages guided the isolation of nine prenylated isoflavones, including a new cudraisoflavone L (1) and eight known metabolites furowanin B (2), erysubin A (3), wighteone (4), lupalbigenin (5), laburnetin (6), isolupalbigenin (7), 6,8-diprenylorobol (8), millewanin H (9) from the leaves of Cudrania tricuspidata. At the concentration of 10 µM, compounds 1, 2, and 4 significantly inhibited NO production with the inhibitory values of 72.5 ± 2.4, 66.9 ± 1.8, and 55.4 ± 2.7%, respectively. In addition, all of isolated compounds 1-9 showed promising cytotoxic effects toward HL-60 cells (IC50 4.3 ± 0.7 to 18.0 ± 1.7 µM).

Anti-inflammatory coumarins from Paramignya trimera.

CONTEXT: Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated. OBJECTIVE: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds. MATERIALS AND METHODS: Cytotoxicity of isolated compounds (5-40 µM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 µM) on nitrite and PGE2 concentrations were determined using Griess reaction and PGE2 ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 µM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS). RESULTS: Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6',7'-dihydroxy-3',7'-dimethylocta-2'-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1-4 and 7 inhibited NO and PGE2 production in LPS-stimulated BV2 cells, with IC50 values ranging from 9.8 to 46.8 and from 9.4 to 52.8 µM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression. DISCUSSION AND CONCLUSION: The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.