Phenolic Glycosides from the Leaves of Iodes cirrhosa Turcz. with Cytotoxic and Antimicrobial Effects.

In the present study, 14 phenolic glycosides, including one new neolignan glycoside, iodescirrhoside A (1), three new flavonol glycosides, iodescirrhosides B-D (2-4), and 10 known metabolites were obtained from the methanol extract of Iodes cirrhosa leaves. Structural elucidation was performed by interpretating the 1D- and 2D- NMR, HR-ESI-MS, and CD spectra in comparison with literature data. All compounds were noncytotoxic to LU-1, HepG2, MCF-7, SK-Mel-2, and LNCaP cancer cell lines. Compound 11 significantly inhibited the growth of E. faecalis. In contrast, weak inhibition was observed for 1-9 and 14 against E. faecalis, for 1, 6-8, and 11 against S. aureus, for 6 and 13 against B. cereus, and 2, 4, and 6-9 against C. albicans.

Chemical constituents from Vietnamese mangrove Calophyllum inophyllum and their anti-inflammatory effects.

In a search for anti-inflammatory activity in resources from Vietnamese mangroves, we found that a methanolic extract from the leaves of Calophyllum inophyllum (CIL) showed significant anti-inflammatory effects in vitro. Using various chromatographic techniques, we subsequently isolated 12 compounds (1-12) from a methanolic extract of CIL, including two novel compounds (1-2). The inhibitory effects of these compounds on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were also evaluated. Compound 1 significantly suppressed NO production (IC50 = 2.44 ±â€¯0.88 µM), the secretion of pro-inflammatory cytokines (including interleukin-1 beta and tumor necrosis factor alpha), and the expression of inducible nitric oxide synthase through downregulation of nuclear factor-kappa-B signaling cascades. These results suggest that C. inophyllum leaves might be a useful resource for the development of drugs for the treatment of inflammation.

Three new flavonol glycosides from Fissistigma pallens.

Three new flavonol glycosides, fissflavosides A-C (1-3), together with six known flavonol glycosides, kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-galactopyranoside (4), kaempferol 3-O-α-L-rhamnopyranosyl-(1→6)-ß-D-galactopyranoside (5), kaempferol 3-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranoside (6), rhamnetin 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside (7), rutin (8), and isorhamnetin 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-galactopyranoside (9) were isolated from the methanol extract of the Fissistigma pallens leaves. Their chemical structures were determined by 1D-, 2D-NMR, and MS data as well as in comparison with reported data in the literature. Compounds 1-9 showed weak cytotoxic activity on three human cancer cell lines, HT-29, A-2058, A-549 with IC50 ranging from 134.6 to 162.6 µM. In addition, the antioxidant capacities of compounds were also tested by ORAC assay. All compounds showed significant antioxidant with trolox equivalents ranging from 4.4 to 8.6 µM at the concentration of 1.0 µM. The results indicated 7 and 8 having meaningful reducing capacity of copper (I) ions of 2.7 to 6.9 µM at the concentrations of 1 and 2 µM.

Achievements in the Study of Marine Low-Molecular Weight Biologically Active Metabolites from the Vietnamese Territorial Waters as a Result of Expeditions aboard the Research Vessel 'Akademik Oparin' (2004-2017).

Until 2004, the secondary metabolites of marine organisms of the Vietnamese territorial waters had been studied very poorly. Only four new compounds were isolated from 1977 to 2003. Joint Russian-Vietnamese expeditions aboard the research vessel 'Akademik Oparin' made it possible to study in detail the chemical diversity of marine micro- and macroorganisms. As a result of five expeditions, more than 250 low-molecular weight natural compounds, including 117 new metabolites, were isolated from marine invertebrates and microfilamentous fungi. Their biological activities, such as cytotoxic, cytoprotective, and antioxidant activities, were investigated. Information about the structure and biological activity of the compounds, the source for their isolation and the geographical location of the objects is summarized in this review.

Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus.

BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S) 5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S) 5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.

Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals.

Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds.

Synthesis of chromonylthiazolidines and their cytotoxicity to human cancer cell lines.

Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 µg/mL) and breast cancer (IC50 32.8 ± 1.4 µg/mL) cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.

Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 µg/mL). Among the compounds isolated from these extracts, laevigatol B (1) from Lobophytum crassum and L. laevigatum, (24S)-ergost-4-ene-3-one (2) from Sinularia dissecta, astropectenol A (3) from Astropecten polyacanthus, and cholest-8-ene-3ß,5α,6ß,7α-tetraol (4) from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 µM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 µM). Laevigatol B (1) and 5α-cholest-8(14)-ene-3ß,7α-diol (5) exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

Anti-inflammatory components of the starfish Astropecten polyacanthus.

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 µM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 µM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 µM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 µM) and 6 (IC50 = 79.05 ± 2.05 µM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 µM) and 4 (IC50 = 16.73 ± 0.25 µM) moderately inhibited the production of TNF-α and IL-6, respectively.

Acylated flavonoid glycosides from Barringtonia pendula and their inhibition on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Six new acylated flavonoid glycosides namely barringosides J - O (1-6) along with tephrokaempferoside and barringoside D were isolated from the branches and leaves of Barringtonia pendula. The structural elucidation was confirmed by extensive analysis of their spectroscopic data including HRQTOFMS, 1D and 2D NMR experiments. Moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells were observed for barringosides M (4) and N (5) with IC50 values of 48.40 ± 3.01 and 56.61 ± 3.87 µM, whereas weak inhibition was found for compounds 1-3, 6, and 7 with IC50 values ranging from 64.91 ± 3.68 to 79.80 ± 3.90 µM.

Cembranoids from the Vietnamese soft coral Sarcophyton ehrenbergi.

Using various chromatographic separations, two new cembranoids, ehrenbergols F and G (1 and 2), along with three known analogs ehrenbergol D (3), (+)-isosarcophine (4) and sinulariol Z2 (5) were isolated from the soft coral Sarcophyton ehrenbergi. The structural elucidation was done by extensive analysis of the 1 D and 2 D NMR, HR-ESI-QTOF-MS as well as CD experiments. In addition, compounds 1 (IC50 of 38.38 ± 2.89 µM), 3 (IC50 of 37.14 ± 3.22 µM) and 4 (IC50 of 45.01 ± 2.49 µM) revealed moderate inhibitory activity on LPS-induced NO production in RAW264.7 cells, whereas 2 (IC50 of 73.32 ± 1.95 µM) and 5 (IC50 of 64.48 ± 4.93 µM) exhibited weak effect.

Phenolic glycosides from Oroxylum indicum.

Two new phenolic glycosides, oroxylumosides A (1) and B (2), along with four known compounds darendoside A (3), leucosceptoside A (4), acteoside (5) and decaffeoylacteoside (6) were isolated from the stem bark of Oroxylum indicum. Their structures were elucidated by extensive analysis of the 1 D and 2 D NMR as well as HR-ESI-QTOF-MS. In addition, compounds 1 - 4 exhibited inhibitory effects on NO production in LPS-stimulated BV2 microglial cell line with IC50 values of 58.2 ± 2.9, 70.6 ± 3.5, 56.8 ± 2.8 and 61.1 ± 3.1 µM, respectively.

Phenylpropanoids from the leaves of Acanthopanax koreanum and their antioxidant activity.

By various chromatographic methods, one new phenylpropanoid, acanthopanic acid (1), and three known compounds, 1,2-O-dicaffeoylcyclopenta-3-ol (2), (4S)-α-terpineol 8-O-ß-D-glucopyranoside (3), and rutin (4), were isolated from the methanol extract of the Acanthopanax koreanum leaves. Their structures were elucidated on the basis of spectroscopic analyses, and their antioxidant activities were evaluated by the intracellular reactive oxygen species (ROS) radical scavenging 2',7'-dichlorofluorescein diacetate assay. Among them, compounds 1, 2, and 4 showed significant scavenging capacity with IC(50) values of 3.8, 2.6, and 2.9 µM, respectively, and compound 3 showed weak scavenging capacity with the inhibition rate of 37% at 40 µM.

Prenylated flavonoids and other constituents from Macaranga indica.

Four new prenylated flavonoids, macarindicins I-IV (1-4) together with ten known compounds, broussoflavonol F (5), vedelianin (6), schweinfurthin E (7), vitexin (8), 2″-rhamnosyl vitexin (9), isovitexin (10), (6R,7E,9R)-9-hydroxy-megastigman-4,7-dien-3-one-9-O-ß-D-glucopyranoside (11), 6S,9R)-roseoside (12), (6S,9S)-roseoside (13), and bridelionoside B (14) were isolated from the leaves of Macaranga indica. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR, and MS data. All the isolated compounds were evaluated for their cytotoxic activities against four human cancer cell lines including KB, MCF-7, HepG-2, and LU. As a result, compound 6 significantly exhibited cytotoxic activity against all tested human cancer cell lines with IC50 values ranging from 4.7 to 11.0 µM. Compounds 2, 5, and 7 showed moderate cytotoxic activity with IC50 values ranging from 7.0 to 38.7 µM.

Cytotoxic and immunomodulatory phenol derivatives from a marine sponge-derived fungus Ascomycota sp. VK12.

Chemical investigation of the marine-derived endophytic fungus Ascomycota sp. VK12 resulted in isolation and identification of a new compound, (3R)-(3',5'-dihydroxyphenyl)butan-2-one (1) and five known ones: AGI-7 (2), sescandelin (3), sescandelin-B (4), 4-hydroxybenzaldehyde (5), and hydroxysydonic acid (6). The absolute configuration of 1 was determined by time-dependent density functional theory electronic circular dichroism, specific optical rotation, and NMR calculations. Compounds 1 and 2 showed cytotoxicity towards HepG2, MCF-7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 48.6 to 96.5 µM. Compounds 1, 2, 4-6 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values in a range from 24.2 to 76.5 µM. Compound 2 further inhibited PGE2 overproduction, with an IC50 value of 25.3 µM. The inhibitory effects of 2 towards NO and PGE2 overproduction were found to have a close relationship with its suppression of iNOS and COX-2 protein expression, respectively.

Four new pregnane glycosides from Gymnema latifolium and their α-glucosidase and α-amylase inhibitory activities.

Four new pregnane glycosides, gymlatifosides A - D (1 - 4) and one known pregnane glycoside, verticilloside J (5) were isolated from the leaves of Gymnema latifolium Wall. ex Wight. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, HR-ESI-MS, and in comparison with the reported data. All these compounds were tested for α-glucosidase and α-amylase inhibitory activities. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 37.8 ± 1.5% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 7.0 to 30.1%. In addition, all compounds 1-5 showed moderate/weak anti α-amylase activity in the investigated test.

Three new muurolane-type sesquiterpene glycosides from the whole plants of Balanophora fungosa subsp. indica.

Three new muurolane type sesquiterpene glycosides, named balanoindicosides A - C (1 - 3), were isolated from the whole plant of Balanophora fungosa subsp. indica using various chromatographic methods. Their structures were determined by extensive analysis of HR-ESI-MS and NMR spectroscopy. The stereochemistry of muurolane sesquiterpene backbone was demonstrated by NOESY analysis. Configuration of C-12 in compounds 2 and 3 could be distinguished by chemical shift value of C-14. Compounds 1-3 exhibited weak cytotoxic activity towards HepG-2, HL-60, LU-1, and MCF-7 cell lines.

Cytotoxic sesquiterpene glucosides from Fissistigma pallens.

Six undescribed sesquiterpene glucosides, fissispallins A-F, and one known sesquiterpene glucoside, fissispallin, were discovered in the leaves of Fissistigma pallens (Finet & Gagnep.) Merr. The structures were determined using spectroscopic methods, including 1D, 2D NMR, and MS. All compounds were evaluated for cytotoxic activity against three human cancer cell lines, HT-29, A-2058, and A-549. Fissispallin A showed potent activity with the IC50 values less than 1.5 µM against all tested human cancer cell lines. Fissispallin also showed potent activity with IC50 value of 0.4 ± 0.3 on the A-2058 cancer cell lines. Fissispallins B-D showed significant cytotoxic activity against all the tested cancer cell lines with IC50 values ranging from 3.8 to 7.2 µM.

Polyphenols isolated from antiradical extracts of Mallotus metcalfianus.

Six flavonoids including two new flavones, luteolin 7-O-(4''-O-(E)-coumaroyl)-beta-glucopyranoside), chrysoeriol-7-O-(4''-O-(E)-coumaroyl)-beta-glucopyranoside) and a mixture of two pairs of diastereoisomeric flavonolignans, (+/-)-hydnocarpin 7-O-(4''-O-(E)-coumaroyl)-beta-glucopyranoside)/(+/-)-hydnocarpin-D 7-O-(4''-O-(E)-coumaroyl)-beta-glucopyranoside) with a 2:1 ratio were isolated from the whole plant of Mallotus metcalfianus Croizat, in addition to 10 known compounds. Their structures were evaluated on the basis of different spectroscopic methods, including extensive 1D and 2D NMR spectroscopy. Some extracts have moderate antimicrobial properties and interesting antiradical (DPPH) activity, as well as some compounds isolated from this species. Tannins were also identified in some active extracts.