Cytotoxic Alkaloids from Leaves of Pilea aff. martinii.

Two new phenanthroquinolizidine alkaloids (1: and 2: ) and a new piperidine derivative (3: ) were isolated from the leaves of Pilea aff. martinii together with 3 known alkaloids: julandine (4: ), cryptopleurine (5: ), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (6: ). Their structures were determined by spectral data analyses including mass spectrometry and 2-dimensional nuclear magnetic resonance data. The absolute configurations of 1: -3: were established by comparison of their experimental circular dichroism data with the calculated electronic circular dichroism spectra. The isolated compounds were evaluated for their cytotoxicity against 4 cancer cell lines: KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). The new phenanthroquinolizidine pileamartine D (2: ) showed strong and selective proliferation inhibition toward KB and HepG-2 cells with IC50 values of 25 and 27 nM, respectively. Pileamartine C (1: ), julandine (4: ), and cryptopleurine (5: ) exhibited cytotoxicity against 4 tested cancer cell lines with IC50 values less than 1 µM.

Antimicrobial Lavandulylated Flavonoids from a Sponge-Derived Streptomyces sp. G248 in East Vietnam Sea.

Three new lavandulylated flavonoids, (2S,2''S)-6-lavandulyl-7,4'-dimethoxy-5,2'-dihydroxylflavanone (1), (2S,2''S)-6-lavandulyl-5,7,2',4'-tetrahydroxylflavanone (2), and (2''S)-5'-lavandulyl-2'-methoxy-2,4,4',6'-tetrahydroxylchalcone (3), along with seven known compounds 4-10 were isolated from culture broth of Streptomyces sp. G248. Their structures were established by spectroscopic data analysis, including 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configurations of 1-3 were resolved by comparison of their experimental and calculated electronic circular dichroism spectra. Compounds 1-3 exhibited remarkable antimicrobial activity. Whereas, two known compounds 4 and 5 exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 6.0 µg/mL and 11.1 µg/mL, respectively.

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii.

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.

Chemical Composition and Biological Activities of Metabolites from the Marine Fungi Penicillium sp. Isolated from Sediments of Co To Island, Vietnam.

Marine microorganisms are an invaluable source of novel active secondary metabolites possessing various biological activities. In this study, the extraction and isolation of the marine sediment Penicillium species collected in Vietnam yielded ten secondary metabolites, including sporogen AO-1 (1), 3-indolecarbaldehyde (2), 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3), 2-[(2R-hydroxypropanoyl)amino]benzamide (4), 4-hydroxybenzandehyde (5), chrysogine (6), 3-acetyl-4-hydroxycinnoline (7), acid 1H-indole-3-acetic (8), cyclo (Tyr-Trp) (9), and 2',3'-dihydrosorbicillin (10). Their structures were identified by the analysis of 1D and 2D NMR data. Among the isolated compounds, 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3) showed a strong inhibitory effect against Enterococcus faecalis with a minimum inhibitory concentration value of 32 µg/mL. Both 2-[(2R-hydroxypropanoyl)amino]benzamide (4) and 4-hydroxybenzandehyde (5) selectively inhibited E. coli with minimum inhibitory concentration values of 16 and 8 µg/mL, respectively. 2',3'-Dihydrosorbicillin (10) potentially inhibited α-glucosidase activity at a concentration of 2.0 mM (66.31%).

New 9α-Hydroxy-5α,6α-epoxyhydroxysterols from the Vietnamese Marine Sponge Ircinia echinata.

Chemical investigation of the methanol extract of the Vietnamese marine sponge Ircinia echinata led to the isolation of six new 9α-hydroxy-5α,6α-epoxysterols: 5α,6α-epoxycholesta-7,22(E)-dien-3ß,9α-diol (1), 5α,6α-epoxycholesta-7,24(28)-dien-3ß,9α-diol (2), (24R)-5α,6α-epoxy-24-ethyl-cholesta-7-en-3ß,9α-diol (3), 5α,6α-epoxycholesta-7-en-3ß,9α-diol (4), (24S)-5α,6α-epoxyergosta-7,22-dien-3ß,9α-diol (5), and (24R)-5α,6α-epoxy-24-methyl-cholesta-7-en-3ß,9α-diol (6) along with the known 5α-6α-epoxysterols: 5α,6α-epoxystigmasta-7-en-3ß-ol (7), 5α,6α-epoxystigmasta-7,22-dien-3ß-ol (8), and 5α,6α-epoxyergosta-7-en-3ß-ol (9). Their structures and their configurations were established on the basis of high resolution mass spectra and extensive 1D and 2D NMR spectroscopic data and by comparison with the literature. Their cytotoxic activity, evaluated against three human cancer cell lines, MCF-7, Hep-G2 and LU-1, revealed that only compounds 3 and 4 exhibited significant antiproliferative activity and compound 3 showed a selective inhibition towards the MCF-7 human breast cancer cells.

Cytotoxic dammarane-type triterpenoids from the leaves of Viburnum sambucinum.

Four new dammarane-type triterpenoids (1-4) and twelve known compounds (5-16) were isolated from the leaves of Viburnum sambucinum Reinw. ex Blume. Their structures were determined by spectral data analysis, including MS and 2D NMR. Cytotoxic activity evaluation in vitro against four cancer cell lines (KB, LU-1, HepG2 and MCF7) suggested that the octanor-dammarane derivatives were the main cytotoxic components of the leaves of V. sambucinum.

Two new sesquiterpenes from the fruits of Fissistigma villosissimum.

Two new sesquiterpenes, namely fissistinone (1) and fissistinol (2), along with ten known compounds (3-12), were isolated from the fruits of Fissistigma villosissimum. Their structures were elucidated on the basis of spectral data analysis, including one-dimensional (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). Compounds 1-8 were evaluated for their cytotoxic activities against KB cell line; however, all these compounds did not show cytotoxic activity.

Cytotoxic steroid derivatives from the Vietnamese soft coral Sinularia brassica.

Using various chromatographic separations, six ergostane-type steroids, including one new compound sinubrassione (1), and two pregnene-type steroid glycosides, including one new compound sinubrassioside (7), were isolated from methanol extract of the Vietnamese soft coral Sinularia brassica. The structure elucidation was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-MS. The cytotoxic activities of all the isolated compounds against three human cancer cell lines were also evaluated using MTT-based colorimetric assays.

7-Methoxy-(9H-ß-Carbolin-1-il)-(E)-1-Propenoic Acid, a ß-Carboline Alkaloid From Eurycoma longifolia, Exhibits Anti-Inflammatory Effects by Activating the Nrf2/Heme Oxygenase-1 Pathway.

Eurycoma longifolia is an herbal medicinal plant popularly used in Southeast Asian countries. In the present study, we show that 7-methoxy-(9H-ß-carbolin-1-il)-(E)-1-propenoic acid (7-MCPA), a ß-carboline alkaloid isolated from E. longifolia, exerted anti-inflammatory effects by activating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. 7-MCPA inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO), prostaglandin E2 (PGE2 ), and interleukin-6 (IL-6) in RAW264.7 cells and rescued C57BL/6 mice from LPS-induced lethality in vivo. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6 was also significantly suppressed by treatment of 7-MCPA in RAW264.7 cells. 7-MCPA induced nuclear translocation of Nrf2 and increased transcription of its target genes, such as HO-1. Treating RAW264.7 cells with 7-MCPA increased the intracellular level of reactive oxygen species (ROS) and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK); however, co-treatment with the antioxidant N-acetyl-cysteine (NAC) blocked 7-MCPA-induced p38 MAPK phosphorylation. Moreover, NAC or SB203580 (p38 MAPK inhibitor) blocked 7-MCPA-induced nuclear translocation of Nrf2, suggesting that 7-MCPA activated Nrf2 via a ROS-dependent p38 pathway. 7-MCPA induced HO-1 protein and mRNA expression and knockdown of Nrf2 with siRNA or SB203580 blocked 7-MCPA-mediated induction of HO-1 expression. Inhibiting Nrf2 or HO-1 abrogated the anti-inflammatory effects of 7-MCPA in LPS-stimulated RAW264.7 cells. We also demonstrated that 7-MCPA suppressed LPS-induced nuclear factor κB (NF-κB) activation. These results provide the first evidence that 7-MCPA exerts its anti-inflammatory effect by modulating the Nrf2 and NF-κB pathways and may be a potential Nrf2 activator to prevent or treat inflammatory diseases.

Endiandric acid analogues from Beilschmiedia ferruginea as dual inhibitors of Bcl-xL/Bak and Mcl-1/Bid interactions.

A rapid screening by (1)H and (1)H-(13)C HSQC NMR spectroscopy of EtOAc extracts of Endiandra and Beilschmiedia species allowed the selection of Beilschmiedia ferruginea leaves and flowers extract for a chemical investigation, leading to the isolation of 11 new tetracyclic endiandric acid analogues, named ferrugineic acids A-K (1-11). Their structures were determined by 1D and 2D NMR spectroscopic analysis in combination with HRMS data. These compounds were assayed for Bcl-xL and Mcl-1 binding affinities. Ferrugineic acids B, C, and J (2, 3, and 10) exhibited significant binding affinity for both antiapoptotic proteins Bcl-xL (Ki = 19.2, 12.6, and 19.4 µM, respectively) and Mcl-1 (Ki = 14.0, 13.0, and 5.2 µM, respectively), and ferrugineic acid D (4) showed only significant inhibiting activity for Mcl-1 (Ki = 5.9 µM).

Cytotoxic aryltetralin lignans from fruits of Cleistanthus indochinensis.

Eight new aryltetralin lignans, cleisindosides A-F (1-6), picroburseranin (7), and 7-hydroxypicropolygamain (8), were isolated from the fruits of Cleistanthus indochinensis (Euphorbiaceae). The structures of the isolates were established on the basis of their one- and two-dimensional NMR spectral data, as well as their mass spectrometric data. Compound 7 was found to have potent cytotoxicity against oral epidermoid carcinoma cells with an IC50 value of 0.062 µM, whereas glycosylation to 3 (IC50 7.5 µM) and stereochemical changes to 8 (IC50 10.8 µM) led to marked decreases in biological activity. Thus, it was determined that the C-7 and C-8' positions are critical for the biological activity of the lignans from this plant.

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus.

CONTEXT: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion. OBJECTIVE: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase. MATERIALS AND METHODS: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays. RESULTS: A new (2RS,3SR)-3,4',5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. DISCUSSION: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents. CONCLUSION: The isolated compounds may contribute to the antidiabetic property of C. rotundus.

Antifouling 26,27-cyclosterols from the Vietnamese marine sponge Xestospongia testudinaria.

Three new C29 sterols with a cyclopropane ring cyclized between C-26 and C-27 of the side chain, aragusterol I (1), 21-O-octadecanoyl-xestokerol A (4), and 7ß-hydroxypetrosterol (5b), were isolated from the Vietnamese marine sponge Xestospongia testudinaria, along with the known compounds, aragusterol B (2), xestokerol A (3), 7α-hydroxypetrosterol (5a), 7-oxopetrosterol (6), and petrosterol (7). The structures of the new compounds were established by analysis of spectroscopic data including 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry (HRESIMS). Their capacity to inhibit the adhesion of isolated bacteria from marine biofilms was evaluated against the bacterial strains Pseudoalteromonas sp. D41, Pseudoalteromonas sp. TC8, and Polaribacter sp. TC5. Aragusterol B (2) and 21-O-octadecanoyl-xestokerol A (4) exhibited the most potent antifouling activity with EC50 values close to these reported in the literature for tributyltin oxide, a marine anti-biofouling agent now considered to be a severe marine pollutant. Due to its comparable activity to tributyltin oxide and its absence of toxicity, the new 26,27-cyclosterol, 21-O-octadecanoyl-xestokerol A (4) constitutes a promising scaffold for further investigations.

Cytotoxic lignans from fruits of Cleistanthus indochinensis: synthesis of cleistantoxin derivatives.

Two new aryl-tetralin lignans, 1 and 2, were isolated from the fruits of Cleistanthus indochinensis by bioassay-guided purification. Their structures were determined by spectroscopic analysis including MS and 2D NMR. The absolute configurations of 1 and 2 were established from examination of their CD spectra. Compound 1 was cytotoxic against KB cells with an IC(50) value of 0.022 µM, while compound 2 had weaker cytotoxicity, with an IC(50) value of 1.4 µM. When tested against other cancer cell lines (MCF-7, MCF-7R, and HT29), 1 showed an IC(50) of 0.014 against MCF-7R cells and an IC(50) of 0.036 µM against MCF-7 cells. A series of amide derivatives of a new lactone, homoderivatives of 1, were prepared. Of these derivatives, only compound 3 had weak cytotoxicity against KB cells.

Acetylcholinesterase inhibitors from the leaves of Macaranga kurzii.

Bioassay-guided fractionation of an extract of leaves of Macaranga kurzii yielded four new compounds, a stilbene (furanokurzin, 1) and three flavonoids (macakurzin A-C, 2-4). Nine known compounds were also isolated (5-13). Their structures were determined by spectroscopic analyses including MS and 2D NMR. The isolates were all evaluated for acetylcholinesterase inhibitory activity. Compound 6 (trans-3,5-dimethoxystilbene) exhibited the greatest activity (IC50 9 µM). Cytotoxic evaluation against KB cells showed that compound 7 had an IC50 of 4 µM, followed by 11 (IC50 10 µM) and 3 (IC50 13 µM).

Chalcone-derived Diels-Alder adducts as NF-κB inhibitors from Morus alba.

A bioassay-guided phytochemical fractionation of the methanol extract of the Morus alba root barks led to the isolation of two chalcone-derived Diels-Alder adducts (1 and 2). Their structures were elucidated as kuwanon J 2,4,10″-trimethyl ether (1) and kuwanon R (2) by means of spectroscopic methods. Both compounds strongly inhibited nuclear transcription factor.κB activity with the IC50 values of 4.65 and 7.38 µM, respectively.

Antioxidant activity of a new C-glycosylflavone from the leaves of Ficus microcarpa.

By bioactive-guided fractionation of methanol extract of the Ficus microcarpa leaves, one new C-glucosylflavone, ficuflavoside (1), one new megastigmane glycoside, ficumegasoside (8), and twelve known compounds including flavonoids (2-6), phenylpropanoids (7), megastigmanes (9-11) and sterol derivatives (12-14) were isolated. Their chemical structures were elucidated by mass, 1D, and 2D NMR spectroscopies. The antioxidant activities of these compounds were measured using the oxygen radical absorbance capacity methods. Compounds 1-6 exhibited potent antioxidant activities of 6.6-9.5µM Trolox equivalents at the concentration of 2.0µM. The results indicated 2, 3, and 5 having meaningful reducing capacity of copper (I) ions concentration of 6.1-8.4µM.

Cytotoxic and antioxidant activities of diterpenes and sterols from the Vietnamese soft coral Lobophytum compactum.

Two new diterpenes, lobocompactols A (1) and B (2), and five known compounds (3-7) were isolated from the methanol extract of the soft coral Lobophytum compactum using combined chromatographic methods and identified based on NMR and MS data. Each compound was evaluated for cytotoxic activity against A549 (lung) and HL-60 (acute promyelocytic leukemia) human cancer cell lines. Among them, compound 5 exhibited strong cytotoxic activity against the A549 cell line with an IC(50) of 4.97 ± 0.06 µM. Compounds 3, 4, and 7 showed moderate activity with IC(50) values of 23.03 ± 0.76, 31.13 ± 0.08, and 36.45 ± 0.01 µM, respectively. The cytotoxicity of 5 on the A549 cells was comparable to that of the positive control, mitoxantrone (MX). All compounds exhibited moderate cytotoxicity against the HL-60 cell line, with IC(50) values ranging from 17.80 ± 1.43 to 59.06 ± 2.31 µM. Their antioxidant activity was also measured using oxygen radical absorbance capacity method, compounds 1 and 2 exhibiting moderate peroxyl radical scavenging activity of 1.4 and 1.3 µM Trolox equivalents, respectively, at a concentration of 5 µM.

Cytotoxic steroidal alkaloids from Kibatalia laurifolia.

Four new steroids, 3-epi-gitingensine (1), N-acetylgitingensine (6), kibalaurifoline (7) and kibalaurifenone (8), along with the known paravallarine (2), 7α-hydroxyparavallarine (3), gitingensine (4), and N-methylgitingensine (5) were isolated from the leaves of Kibatalia laurifolia. Their structures were determined primarily from mass spectrometry and 2D NMR analyses. On the basis of the known absolute configurations of 2 and 4, the absolute configurations of the new compounds were proposed. Due to the structural relationships of compounds 1-8, a biosynthetic pathway was suggested. Compound 2 was cytotoxic to KB cells (IC50 12.8 µM), followed by 1 with IC50 21.2 µM.

Lignans and other constituents from the roots of the Vietnamese medicinal plant Pseuderanthemum palatiferum.

Two new lignans, palatiferin A (1) and palatiferin B (2), were isolated from the roots of Pseuderanthemum palatiferum, together with five known triterpenes, epifriedelanol (3), lupeol (4), lupenone (5), betulin (6), pomolic acid (7), and a dipeptide asperglaucide (8). Their structures were established from 2D NMR and mass spectroscopy. The absolute configuration of 1 and 2 was proposed based on the comparison of their optical rotation activities with those of compounds with similar structures such as wodeshiol and paulownin. The new lignans, palatiferin A (1) and palatiferin B (2) exhibited a moderate cytotoxicity against KB and HepG2 cell lines. However, betulin and lupeol, two abundant compounds from the roots of P. palatiferum, showed cytotoxic and antimicrobial activities.