Chemical constituents from the leaves of Sindora siamensis var. maritima and their antimicrobial and α-glucosidase inhibitory activities.

Two new glycosides, sindosides A-B (1-2), along with 11 previously identified metabolites (3-13), were isolated from an ethanolic extract of the leaves of Sindora siamensis var. maritima. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (IR, NMR, and HRMS). The absolute configuration of compound 1 was established by experimental and calculated ECD spectra. The antimicrobial results revealed that compound 8 selectively inhibited C. albicans fungal with a MIC value of 64 µg/mL, whereas 11 presented a weak inhibition toward E. faecalis, S. aureus, and B. cereus bacterial strains with the same MIC value of 128 µg/mL. Interestingly, compounds 1, 2, 8, 9, and 11 showed α-glucosidase inhibitory activity with IC50 values ranging from 14.42 ± 0.21 to 30.62 ± 0.18 µM, which were more active than the positive control (acarbose, with an IC50 value of 46.78 ± 1.37 µM). Enzyme kinetic analysis revealed that compounds 1, 2, and 11 behaved as uncompetitive inhibitors with Ki values of 8.60 ± 1.04, 5.16 ± 0.73, and 7.17 ± 0.98 µM, 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.

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.

Chemical constituents from the branches and leaves of Alchornea annamica.

Phytochemical investigation of the branches and leaves of Alchornea annamica led to isolation of ten secondary metabolites, including two new megastigmane glucosides alnamicosides A (1) and B (2). The structure elucidation was confirmed by 1 D and 2 D NMR, ECD as well as HR-QTOF-MS experiments. The megastigmane derivatives 1 - 3 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 78.72 ± 1.90, 77.40 ± 9.40 and 82.16 ± 4.56 µM, respectively. This is the first report on chemical constituents and biological activity of the plant A. annamica.

Aplydactylonins A-C, three new sesquiterpenes from the Vietnamese sea hare Aplysia dactylomela and their cytotoxicity.

Aplydactylonins A-C (1-3), three new sesquiterpenes, were isolated from the Vietnamese sea hare Aplysia dactylomela. Their structures and absolute configurations were elucidated based on spectroscopic analysis, X-ray crystallography, and density functional theory (DFT) calculations of NMR and ECD data. Compound 2 exhibited cytotoxicity against HepG2, DU145 and A549 cells with respective IC50 values of 4.08 ± 0.63, 38.64 ± 1.04 and 12.33 ± 0.95 µM. In addition, HepG2 cells treated with 5 µM compound 2 for 48 h showed a significant increase in early apoptotic cells (P < 0.05) and increased caspase 3 activity (P < 0.01). Moreover, compound 2 induced sub-G1 phase arrest in HepG2 cells.

Dammarane-type triterpenoid saponins from the flower buds of Panax pseudoginseng with cytotoxic activity.

Phytochemical investigation of a methanol extract of Panax pseudoginseng flower buds resulted in the isolation of 22 dammarane-type triterpenoid saponins, including three new compounds, pseudoginsenosides A-C (1-3), and 19 known analogs. Their chemical structures were identified by the comprehensive spectroscopic methods, including 1 D and 2 D NMR and mass spectra. In addition, their cytotoxic effects toward three human carcinoma cell lines, including liver (HepG2), breast (MCF7), and lung (A549) were also evaluated.

Sesquiterpenoids from Saussurea costus.

Sixteen sesquiterpenoids (1 - 16), including two new compounds namely saussucostusosides A and B (1 and 2), were isolated from the roots of Saussurea costus by various chromatographic separations. Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among isolated compounds, costunlide (6), 3ß-[4-hydroxymethacryloyloxy]-8α-hydroxycostunolide (10) and 11ß,13-dihydrozaluzanin C (16) exhibited potent inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 7.08 ± 0.34, 2.40 ± 0.06 and 5.55 ± 0.24 µM, respectively.

Chemical Constituents from the Branches and Leaves of Alchornea trewioides.

Two new megastigmane glucosides namely trewiosides A (1) and B (2), along with 20α-hydroxypregn-4-en-3-one ß-D-glucopyranoside (3), sugeroside (4), and schizandriside (5) were isolated from the branches and leaves of Alchornea trewioides. The structure elucidation was confirmed by extensive analysis of the one and two dimensional (1 and 2D) NMR, electronic circular dichroism (ECD) as well as high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra. Noteworthily, the isolation of compounds 1 and 2 represents the second finding of megastigmane derivatives with a methoxycarbonyl group at C-5 to date. In addition, compound 3 showed weak cytotoxicity against three human cancer cell lines as A549 (lung carcinoma), HepG2 (hepatocarcinoma), and MCF7 (breast carcinoma). Besides, compounds 2 and 3 exhibited moderate inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Whereas, the remaining compounds 1, 4 and 5 showed weak inhibitory activity.

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.

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.

Acylated flavonoid glycosides from Barringtonia racemosa.

Using various chromatographic separations, three new acylated flavonoid glycosides, namely barringosides G-I (1-3), were isolated from the water-soluble extract of Barringtonia racemosa branches and leaves. The structure elucidation was performed by extensive analysis of the 1D and 2D NMR and HR-QTOF-MS data. Of the isolated compounds, barringoside I (3) showed moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with an IC50 of 52.48 ± 1.04 µM.

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.

Bis-sesquiterpene from the Marine Sponge Dysidea fragilis.

Two new sesquiterpenes and one new bis-sesquiterpene, named dysinidins C-E (1-3) along with three known sterols, dysideasterol F, 9α,l lα-epoxycholest-7-en-3ß,5α,6α-triol, and 9α,11α-epoxycholest-7-en-3ß,5α,6α,19-tetrol 6-acetate (4-6) were isolated from the Vietnamese marine sponge Dysidea fragilis (Montagu, 1814). Their structures were determined by 1D- and 2D-NMR spectroscopies and HR-ESI-MS, as well as by comparison with reported literature data. Compounds 4-6 were found to inhibit eight human cancer cell lines (KB, LU-1, HL-60, LNCaP, SK-Mel-2, HepG-2, MCF-7, and PC-3), with IC50 values ranging from 7.3 to 31.5 µM.

New Phenolic Glycosides from Physalis angulata.

Two new phenolic glycosides, physangulosides A and B (1 and 2), were isolated from the whole plant of Physalis angulata. Their chemical structures were determined by mean of HR-ESI-MS, lD, and 2D-NMR spectra. Both of the compounds showed weak protection against hydrogen peroxide induced hepatocytes damage.

Guaiane Sesquiterpenoids from the Gorgonian Menella woodin.

Two new guaiane derivatives (1 and 2) along with six known sesquiterpenoids (3-8) were isolated from the gorgonian Menella woodin. Their structures -were elucidated by ID and 2D NMR and HRESIMS data as well as by comparison of their spectra with those in the literature. Relative configurations of asymmetric centers in 1 and 2 were suggested on the basis of NOESY and ID NOE correlations, absolute stereochemistry of these compounds was proposed in result of comparison of calculated (for both enatiomers) and experimental ECD. Some suggestions were made regarding a biosynthesis of guaiane sesquiterpenoids in this species. All the compounds were firstly isolated from M woodin.

Two new simple iridoids from the ant-plant Myrmecodia tuberosa and their antimicrobial effects.

Six iridoid derivatives (1-6), including two new compounds myrmecodoides A and B (1 and 2), were isolated from the ant-plant Myrmecodia tuberosa. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY and HR-ESI-MS) and by comparison with the literature values. Among isolates, 3 and 4 exhibit weak antibacterial effect against Staphylococcus aureus subsp. aureus with MIC value of 100.0 µg/mL.

Using the gene expression signature of scutebarbalactone VN isolated from Scutellaria barbata to elucidate its anticancer activities.

Bioassay-guided fractionation led to the discovery of a novel neo-clerodane diterpenoid, scutebarbalactone VN (BalA: 8,13-epoxy-3-en-7-hydroxy-6,11-O- dibenzoyl-15,16-clerodanolide), from the methanol extract of the whole-plant of Vietnamese Scutellaria barbata D. Don. A microarray technique combined with bioinformatic analyses showed that BalA could inhibit cell cycle pathways by downregulating genes such as CDC25A and AURKA. BalA also showed the potential to reactivate downregulated genes in hepatocellular carcinoma cells and genes in antioxidant pathways such as HMOX1 and HSPA1A. Querying Connectivity map 2.0 resulted in a match of the BalA-modulated gene signature with that of 10 known compounds, most of which are currently marketed chemotherapy drugs. The highest matching scores belonged to lomustine, semustine, and withaferin A. Lomustine and semustine were found to alkylate DNA and RNA, while withaferin A inhibits nuclear factor kappa B (NF-κB) activity. A luciferase reporter assay was also conducted on 293/NF-κB human embryonic kidney cells that had been transfected with the NF-κB-luciferase plasmid to verify the anticancer activity of BalA. The assay showed that BalA effectively blocked NF-κB with an IC50 of 38.6 ± 0.05 µM.

Two new naphthalene glucosides and other bioactive compounds from the carnivorous plant Nepenthes mirabilis.

Two new naphthalene diglucosides named nepenthosides A (1) and B (2), together with eleven known compounds (3-13), were isolated from the carnivorous plant Nepenthes mirabilis. The structures of these compounds were elucidated based on extensive spectroscopic analysis, including 1D- and 2D-NMR, and MS. The antioxidant activities of compounds 1-13 were evaluated in terms of their peroxyl radical-scavenging (trolox equivalent, TE) and reducing capacities. All isolates showed peroxyl radical-scavenging and reducing activities at concentrations of 1.0 and 10.0 µM. Anti-osteoporotic activities were investigated using murine osteoclastic RAW 264.7 cells. Compounds 1-7 and 9-12 significantly suppressed tartrate-resistant acid phosphatase activity down to 91.13 ± 1.18 to 42.39 ± 1.11%, relative to the control (100%) in nuclear factor-κB ligand (RANκL)-induced osteoclastic RAW 264.7 macrophage cells.

Chemical constituents from Kandelia candel with their inhibitory effects on pro-inflammatory cytokines production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs).

Chemical investigation of Kandelia candel resulted in the isolation of 19 compounds (1-19), including one new sesquiterpene glycoside, kandelside (1), three megastigman glycoside compounds (7-9), 16 known phenolic compounds (2-6 and 10-19). Structures of the isolated compounds were elucidated based on spectral data comparison with reported values. Isolated compounds were also evaluated for their inhibitory effects on the production of pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among these compounds, compound 9 exhibited strong inhibitory activity against IL-6 production (IC50=0.07 ± 0.05 µM) and moderate inhibitory activity against TNF-α production (IC50=49.86 ± 1.02 µM), but exhibited no activity on IL-12 p40 production. Compounds 5 and 6 significantly inhibited IL-12 p40, IL-6, and TNF-α production with IC50 values of 11.68 ± 0.38, 44.52 ± 1.08, and 28.73 ± 0.96 µM, respectively.