Hyperelatosides A–E,biphenyl ether glycosides from Hypericum elatoides,with neurotrophic activity

Five new biphenyl ether glycosides, hyperelatosides A–E (1–5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7–15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1–15 were preliminarily evaluated in vitro.

Five new biphenyl ether glycosides, hyperelatosides A–E, one new benzoate glycoside, hyperelatoside F, were isolated from Hypericum elatoides. Hyperelatosides A, B, and D–F significantly enhanced NGF-induced neurite outgrowth in PC12 cells.     

Neuroinflammatory inhibitors from Gardneria nutans Siebold & Zuccarini

Two new monoterpene indole alkaloid glycosides nutanoside A–B (1–2), two new phenolic glycoside esters nutanester A–B (6–7), together with five known compounds (3–5, 8–9) were isolated from the ethanol extract of Gardneria nutans Siebold & Zuccarini. Their structures were established on the basis of extensive spectroscopic analysis and TDDFT/ECD calculations. Compounds 1 and 2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids. Compounds 3, 4 and 6 displayed significant inhibitory effects on NO production in over-activated BV2 microglial cells, with the IC₅₀ values of 2.29, 6.36, and 8.78 μM, respectively. Compounds 1, 5, 7 could significantly inhibit the mRNA expression of inflammatory factors TNF-α and IL-6 induced by LPS in BV2 microglial cells at the effective concentration. Moreover, compound 3 exhibited stronger cytotoxicities against U87 and HCT116 cell lines than taxol with IC₅₀ values of 10.58 and 14.60 μM, respectively.

Four new compounds were isolated from G. nutans. Compounds 1–2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids.     

Pycnidiophorones A–D,four new cytochalasans from the wetland derived fungus Pycnidiophora dispersa

Pycnidiophorones A–D (1–4), four new cytochalasans with a rare 5/6/6/5/6 pentacyclic skeleton incorporating the unique 12-oxatricyclo[6.3.1.0^2,7]dodecane core, and six known depsidones (5–10) were isolated from cultures of the wetland-soil-derived fungus Pycnidiophora dispersa. Their chemical structures were unambiguously determined using NMR spectroscopic data. The absolute configurations of 1 and 3 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1–10 showed moderate cytotoxicity against a panel of five human tumor cell lines.

Four new 5/6/6/5/6 pentacyclic cytochalasan pycnidiophorones A–D (1–4) and six known depsidones were identified from the wetland-soil-derived fungus Pycnidiophora dispersa.     

Dalpulapans A–E from the roots of Dalbergia stipulacea

Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb. Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb. An evaluation of cytotoxic activity against HeLa, A549 and normal cell lines using MTT assay was performed. The results showed that R,R-velucarpin A (6) was the most active against HeLa cells with an IC₅₀ value of 10.9 ± 0.42 μM, while fortunately this compound exhibited weak cytotoxicity against normal cells (29.20 ± 1.16 μM). Structures of all isolates were identified from their 1D and 2D NMR spectroscopic data and MS analysis. Experimental and calculated ECD spectra were studied to define the absolute configurations.

Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb.     

Cytotoxic alkaloids from the marine shellfish-associated fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy

Eight different culture media were used to culture shellfish Panopea abbreviate associated fungus Aspergillus sp. XBB-4. In a glucose-peptone-yeast (GPY) culture medium supplied with amino acids, this fungus can produce chemodiversity metabolites. Four new alkaloids including three β-carboline alkaloids, aspercarbolines A–C (1–3) and one piperazinedione, asperdione A (13) along with nine known compounds were isolated. The structures were elucidated mainly based on the NMR, MS, ECD and X-ray single-crystal diffraction data. The possible biosynthetic pathways of aspercarbolines A–C (1–3) were proposed. All compounds (1–13) were evaluated for their cytotoxicity against six cancer cell lines, including human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and SUNE1, and human hepatocellular carcinoma cell lines hepG2 and QGY7701.

Cytotoxic alkaloids from marine fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy.     

Sarcosenones A–C,highly oxygenated pimarane diterpenoids from an endolichenic fungus Sarcosomataceae sp.

Three new highly oxygenated pimarane diterpenoids, sarcosenones A–C (1–3), and the known 9α-hydroxy-1,8(14),15-isopimaratrien-3,7,11-trione (4), were isolated from cultures of an endolichenic fungus Sarcosomataceae sp. Their structures were elucidated based on NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compound 1 showed moderate cytotoxicity against a small panel of four human tumor cell lines, with IC₅₀ values of 7.5–26.4 μM.

The new highly oxygenated pimarane diterpenoids sarcosenones A–C (1–3) were isolated from an endolichenic fungus Sarcosomataceae sp. Compound 1 showed moderate cytotoxicity towards human tumor cells.     

Jejucarbazoles A–C,carbazole glycosides with indoleamine 2,3-dioxygenase 1 inhibitory activity from Streptomyces sp. KCB15JA151

A bioassay-guided investigation led to the isolation of three new carbazole glycosides, jejucarbazoles A–C (1–3), from Streptomyces sp. KCB15JA151. Their planar structures were elucidated by detailed NMR and MS spectroscopic analysis with a literature study. Their relative and absolute configurations were established by ROESY correlations, coupling constants, LC-MS analysis of thiocarbamoyl-thiazolidine carboxylate derivatives, and ECD calculation. Compounds 1–3 showed indoleamine 2,3-dioxygenase 1 (IDO1) inhibitory activity with IC₅₀ values of 18.38, 9.17, and 8.81 μM. The molecular docking analysis suggested that all compounds act as heme-displacing inhibitors against IDO1 enzyme.

This study presents the isolation and structure elucidation of jejucarbazoles A–C, isolated from Streptomyces sp. KCB15JA15 and their inhibitory effect and molecular docking analysis against the IDO1 enzyme.     

Xylopins A–F,six rare guaiane dimers with three different connecting modes from Xylopia vielana

Six rare guaiane-type sesquiterpene dimers xylopins A–F, having three different connecting modes through two direct C–C bonds, were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOESY analysis, Cu Kα X-ray crystallography, and experimental and calculated electronic circular dichroism spectra. Flow cytometry demonstrated the fact that compound 6 arrested the cell cycle at G2 phase and concentration-dependently induced apoptosis of DU145 cells. Furthermore, the EPT2-TGC cell model, zebrafish study and western blot analysis illustrated compound 6 could induce apoptosis by efficiently inhibiting the Wnt/β-catenin signaling pathway via decreasing the expression of β-catenin.

Six rare guaiane-type sesquiterpene dimers xylopins A–F, having three different connecting modes through two direct C–C bonds, were isolated from the roots of Xylopia vielana.     

Hyperpatulones A–F,polycyclic polyprenylated acylphloroglucinols from Hypericum patulum and their cytotoxic activities

Six new compounds, hyperpatulones A–F (1–6), along with ten additional known related derivatives (7–16), were isolated from Hypericum patulum (Guttiferae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR), X-ray crystallography, electronic circular dichroism (ECD) spectroscopy and Rh₂(OCOCF₃)₄-induced ECD. All compounds were tested for their cytotoxic activities on human HepG-2, HeLa, MCF-7, and A549 cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compound 5 exhibited significant cytotoxicities against HepG-2, HeLa and A549 cell lines with IC₅₀ values of 9.52 ± 0.27, 11.87 ± 0.22 and 12.63 ± 0.12 μM, respectively.

Six new PPAPs (1–6) were isolated from Hypericum patulum and compound 5 exhibited significant cytotoxicities on various tumor cell lines.     

New triterpenoid saponin glycosides from the fruit fibers of Trichosanthes cucumerina L.

Five new triterpenoid saponin glycosides, trichocucumerisides A–E (1–5), together with eleven known compounds (6–16) were isolated from Trichosanthes cucumerina fruit fibers. The structures of the new compounds were elucidated by detailed analysis of NMR and mass spectroscopic data as well as chemical reactions. The anti-inflammatory study against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells shows that compounds 7 and 9 exhibited stronger NO inhibitory activity, with IC₅₀ values of 3.0 and 2.7 μM, respectively, with comparison to positive references Celecoxib and aminoguanidine (IC₅₀ values 75.7 and 75.0 μM, respectively). Compounds 7 and 9 also possessed a greater selectivity index (SI) of approximately 3–4-fold activity than that of the positive references.

The new glycosides 1–5, together with eleven known compounds were isolated. Two compounds exhibited more potent anti-inflammatory activity than Celecoxib and aminoguanidine reference compounds.     

Bioassay-guided purification of sesquiterpenoids from the fruiting bodies of Fomitopsis pinicola and their anti-inflammatory activity

Twelve undescribed sesquiterpenoids, fomitopins A–L (1–12), were isolated via bioassay-guided purification from the bracket fungus Fomitopsis pinicola (Sw.) P. Karst, and this fungus have been reported to exhibit anti-microbial and anti-inflammatory activities. The structures of 1–12 were elucidated by spectroscopic and spectrometric analyses and their absolute configurations were further confirmed by ECD simulations. Ten isolated compounds were evaluated for their anti-inflammatory potential and compound 11 exhibited the most significant inhibition of superoxide anion generation and elastase release with IC₅₀ values of 0.81 ± 0.15 and 0.74 ± 0.12 μM. These newly purified sesquiterpenoids could be potential candidates for further anti-inflammatory studies.

Twelve undescribed sesquiterpenoids, fomitopins A–L (1–12), were isolated via bioassay-guided purification from the bracket fungus Fomitopsis pinicola which has been reported to exhibit anti-microbial and anti-inflammatory activities.     

Three new cardiac glycosides obtained from the roots of Streblus asper Lour. and their cytotoxic and melanogenesis-inhibitory activities

Three new cardiac glycosides strophanthidin-3-O-α-l-rhamnopyranosyl-(1→4)-6-deoxy-β-d-allopyranoside (1), 5βH-16β-acetylkamaloside (2), and mansonin-19-carboxylic acid (3) along with seven known steroids including five cardiac glycosides were isolated from the methanol extracts of Streblus asper Lour. roots. The structures of these compounds were established by spectroscopic analyses. The cytotoxicities of crude extracts and all the isolated compounds were evaluated against four human cancer cell lines (HL60, A549, AZ521, and SKBR3). Furthermore, the selective index (SI) of each compound was measured by the ratio of cytotoxic effect on a normal cell line (WI38) to the cytotoxic effect on cancer cell line (A549). The results suggested that cardiac glycosides (2, 4, and 6–8) exhibited significant cytotoxicities with IC₅₀ values from 0.01 to 3.77 μM as well as high selective index for WI38/A549 (SI 1.50–24.26), and they displayed superior selectivities when compared with the reference cisplatin (SI 1.09). Preliminary structure–activity relationships (SARs) were also discussed regarding the type of C-10 group in the cardiac glycosides being a crucial factor in determining the cytotoxic activities and regarding the sugar moieties having much less of an active role than the type of C-10 group. In addition, the melanogenesis-inhibitory abilities of these compounds were also evaluated. Cardiac glycosides (3 and 6–8) displayed moderate inhibition effects on melanogenesis with melanin content (MC) of 26.22–74.90% at a concentration of 100 μM, thus showing high cell viability (CV: 77.94–111.70%) compared with that of the reference arbutin (MC: 82.50% and CV: 107.60%). Furthermore, western blot analysis of melanogenesis-related proteins suggested that 3 could inhibit melanogenesis by suppressing the protein expressions of TRP-2 and tyrosinase.

The cardiac glycosides isolated from the methanol extracts of Streblus asper Lour. roots indicated potent cytotoxicities and high selective index, and the mechanism of melanogenesis-inhibition was explored.     

New cytotoxic natural products from the marine sponge-derived fungus Pestalotiopsis sp. by epigenetic modification

Four new polyketide derivatives, pestalotiopols A–D (1–4), together with seven known compounds (5–11), were isolated from a chemical-epigenetic culture of Pestalotiopsis sp. The structures and absolute configurations of the new compounds (1–4) were determined by spectroscopic analyses, Mo₂-induced CD, and electronic circular dichroism (ECD) calculations. All the isolated compounds (1–11) were tested for their cytotoxic activities. Among these compounds, compounds 1, 2, 6 and 7 exhibited cytotoxicity against four human cancer cell lines with IC₅₀ values of 16.5–56.5 μM. The structure–activity relationships of compounds (1–11) were examined. The results indicated that both the diol system of the side chain and the aldehyde group might contribute to the cytotoxic activity. The possible biosynthetic pathways for compounds (1–4) were also postulated.

Four new polyketide derivatives, pestalotiopols A–D (1–4), together with seven known compounds (5–11), were isolated from a chemical-epigenetic culture of Pestalotiopsis sp.     

Pseudonectrins A–D,heptaketides from an endophytic fungus Nectria pseudotrichia

Four new heptaketides, pseudonectrins A–D (1–4), and four known compounds (5–8) were isolated from cultures of an endophytic fungus Nectria pseudotrichia. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1–3 and 4 were assigned by electronic circular dichroism calculations and the modified Mosher method, respectively. Compound 1–3 showed moderate cytotoxicity, with IC₅₀ values of 11.6–41.2 μM.

The new heptaketides, pseudonectrins A–D (1–4), were isolated from a plant endophyte Nectria pseudotrichia. Compounds 1–3 showed moderate cytotoxicity towards human tumor cells.     

Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum

Seven undescribed phenylspirodrimane derivatives, stachybochartins A–G (1–7), and four known analogues (8–11) were isolated from the endophytic fungus Stachybotrys chartarum obtained from Pinellia ternata. Stachybochartins A–D are four rare C–C-coupled dimeric derivatives and stachybochartin G features a seco-bisabosqual skeleton. Their structures and configurations were elucidated via spectroscopic analysis, electronic circular dichroism (ECD) calculations, the ECD exciton chirality method and the modified Mosher''s method. Stachybochartins A–D and G displayed cytotoxic activities against MDA-MB-231 breast cancer cells and U-2OS osteosarcoma cells, with IC₅₀ values ranging from 4.5 to 21.7 μM. Stachybochartins C and G exerted strong anti-proliferative activities against U-2OS cells in concentration- and time-dependent manners and induced apoptosis.

The diverse structures and anticancer activities of phenylspirodrimane derivatives are investigated.     

3-Decalinoyltetramic acids from kiwi-associated fungus Zopfiella sp. and their antibacterial activity against Pseudomonas syringae

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp. Their structures with absolute configurations were established by extensive spectroscopic methods and single crystal X-ray diffraction. The compounds possessed rare pentacyclic systems that might derive from a polyene precursor via [4 + 2] intramolecular Diels–Alder reactions. Compounds 1, 2, and 4 showed antibacterial activity against plant pathogen Pseudomonas syringae with MIC values of 64, 32, and 64 μg mL⁻¹, respectively.

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp.     

New bioactive cyclopeptide alkaloids with rare terminal unit from the root bark of Ziziphus cambodiana

Six new 14-membered ring cyclopeptide alkaloids, cambodines A–F (1–6), and two known compounds, frangufoline (7) and lotusanine B (8), were isolated from the root bark extract of Ziziphus cambodiana Pierre. Their structures and configurations were established based on 1D and 2D NMR, HRMS, ECD, and X-ray crystallographic data. Compounds 1 and 3 are rare 5(14)-type cyclopeptide alkaloids that possess an imidazolidin-4-one ring in the terminal unit. The cyclopeptides were tested for their in vitro antiplasmodial, antitubercular, and cytotoxic effects against three cancer cell lines. Compound 3 showed significant antiplasmodial activity against the malarial parasite Plasmodium falciparum, with an IC₅₀ value of 6.09 μM.

Six new 14-membered ring cyclopeptide alkaloids, cambodines A–F (1–6), and two known compounds, frangufoline (7) and lotusanine B (8), were isolated from the root bark extract of Ziziphus cambodiana Pierre.     

New withanolides from Physalis minima and their cytotoxicity against A375 human melanoma cells

Seven previously undescribed withanolides, namely physaminilide A–G (1–7), and two artificial withanolides (8–9), along with 10 known analogues (10–19) were isolated from Physalis minima. The structures were established by spectroscopic analysis, including NMR and electronic circular dichroism (ECD) data. Cytotoxicity of all the isolates was evaluated against A375 human melanoma cells. Compounds 2, 5, 8, 10, 11 and 15 exhibited significant cytotoxic activities with IC₅₀ values in the range of 1.2–9.4 μM.

The new withanolides physaminilide A–G (1–7), and two artificial withanolides (8–9) were isolated from Physalis minima. Compounds 2, 5 and 8 exhibited significant cytotoxicity towards human tumor cells.     

Guaiane sesquiterpenes from the gorgonian Echinogorgia flora collected in the South China Sea

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A–C (2–4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD and DP4+ probability analyses.

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A–C (2–4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea.     

New α-pyrones from an endophytic fungus,Hypoxylon investiens J2

Four new α-pyrones, hypotiens A–D (1–4), were isolated from a fungal endophyte, Hypoxylon investiens J2, harbored in the medicinal plant Blumea balsamifera. Their structures were determined through detailed HRMS and NMR spectroscopic data. Compounds 1–4 are new α-pyrone derivatives containing an unusual dimethyl substitution in the highly unsaturated side chain. Their plausible biosynthetic pathway was discussed. Biological assay indicated that compounds 1–4 showed no antimicrobial, quorum sensing inhibitory, and cytotoxic activities. The specific side chain in α-pyrone derivatives 1–4 might be responsible for the weak pharmacological activities.

Four new α-pyrones, hypotiens A–D (1–4), were isolated from a fungal endophyte, Hypoxylon investiens J2, harbored in the medicinal plant Blumea balsamifera.