Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85.

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (1-5), along with three known analogues (6-8), were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra. Cytotoxicity assay results indicated that compound 8 had strong cytotoxicity against HeLa cancer cells, and its IC50 value was 11.8 µM. In addition, flow cytometry analysis revealed that the cytotoxicity of 8 was due to the induction of G1 cell cycle arrest and apoptosis in HeLa cells.

Asperphenyltones A and B: New Phenylfuropyridinone Skeleton from an Endophytic Aspergillus sp. GXNU-A1.

Chemical investigation of the fermentation extract of the mangrove endophytic fungus Aspergillus sp. GXNU-A1, isolated from Acanthus ilicifolius L., discovered an undescribed pair of enantiomers (asperphenyltones A and B (±1)), together with four previously described metabolites: nodulisporol (2), isosclerone (3), 2,3,4-trihydroxy-6-(hydroxymethyl)-5-methylbenzyl alcohol (4), and 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (5). Analyses of the 1D and 2D NMR spectroscopic data of the compounds supported their structural assignments. The presence of the asperphenyltones A and B, which are a pair of enantiomers, was established by HR-ESI-MS, 1D and 2D NMR data and confirmed by single-crystal X-ray diffraction analysis. Metabolites 1-5 were evaluated for their anti-inflammatory effects on the production of nitric oxide (NO), and 1, 3, and 4 showed significant potential inhibitory activities against NO production in activated macrophages with IC50 values of 26-40 µM, respectively.

α-Glucosidase inhibitory and anti-inflammatory activities of dammarane triterpenoids from the leaves of Cyclocarya paliurus.

Diabetes mellitus is caused by chronic inflammation and affects millions of people worldwide. Cyclocarya paliurus leaves have been widely used in traditional folk tea as a remedy for diabetes, but the antidiabetic constituents remain to be further studied. The α-glucosidase inhibitory and anti-inflammatory activities were examined to evaluate their effects on diabetes mellitus, and bioassay-guided separation of C. paliurus leaves led to the identification of twenty dammarane saponins, including eleven new dammarane saponins (1-11). The structures of the isolates were elucidated by spectroscopic methods. Bioactivity assay results showed that compounds 1 and 2 strongly inhibited α-glucosidase activity, with IC50 values ranging from 257.74 µM, 282.23 µM, and strongly inhibited the release of NO, with IC50 values of 9.10 µM, 9.02 µM. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1ß, NF-κB, IL-6 and TNF-α in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-κB/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest α-glucosidase inhibitory and anti-inflammatory activities. In addition, the structure-activity relationships (SARs) of the dammarane saponins were investigated. In summary, C. paliurus leaves showed marked α-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating α-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.

Polyketide Derivatives, Guhypoxylonols A-D from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y45 That Inhibit Nitric Oxide Production.

Four undescribed compounds, guhypoxylonols A (1), B (2), C (3), and D (4), were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y45, together with seven previously reported metabolites. The structures of 1-4 were elucidated based on analysis of HRESIMS and NMR spectroscopic data. The absolute configurations of the stereogenic carbons in 1-3 were established through a combination of spectroscopic data and electronic circular dichroism (ECD). Compounds 1-11 were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4, and 6 showed an inhibitory activity against the production of nitric oxide (NO), with the IC50 values of 14.42 ± 0.11, 18.03 ± 0.14, 16.66 ± 0.21, and 21.05 ± 0.13 µM, respectively.

Diaporindenes A-D: Four Unusual 2,3-Dihydro-1 H-indene Analogues with Anti-inflammatory Activities from the Mangrove Endophytic Fungus Diaporthe sp. SYSU-HQ3.

Diaporindenes A-D (1-4), four unusual 2,3-dihydro-1 H-indene isomers, a novel isoprenylisobenzofuran A (5), two new isoprenylisoindole alkaloids diaporisoindoles D and E (6 and 7), and a new benzophenone derivative tenellone D (11), together with four known biogenetic agents (8-10 and 12), were all separated from the endophytic fungus Diaporthe sp. SYSU-HQ3 guided by ultraperformance liquid chromatography high-resolution mass spectrometry. The absolute configurations of 1-7 and 11 were defined by X-ray diffraction, quantum chemical calculations, and spectroscopic analysis. Diaporindenes A-D (1-4) possessed an unprecedented chemical skeleton featuring a 2,3-dihydro-1 H-indene ring and a 1,4-benzodioxan moiety. All of the isolates (1-12) were tested for their inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1-5, 8, and 9 were found to exhibit significant inhibitory effects against nitric oxide production with IC50 values from 4.2 to 9.0 µM and SI values from 3.5 to 6.9. In addition, the structure-activity relationships of all compounds were summarized.

α-Glucosidase Inhibitors: Diphenyl Ethers and Phenolic Bisabolane Sesquiterpenoids from the Mangrove Endophytic Fungus Aspergillus flavus QQSG-3.

Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane sesquiterpenoids (3⁻6), together with five known related derivatives, were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 obtained from a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, China. The structures of compounds 1⁻6 were determined by analyzing NMR and HRESIMS data. The absolute configurations of 5 and 6 were assigned by comparing their experimental ECD spectra with those reported for similar compounds in the literature. All isolates were evaluated for their α-glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11 showed strong inhibitory effects with IC50 values in the range of 1.5⁻4.5 µM.

Alkaloids from the mangrove endophytic fungus Diaporthe phaseolorum SKS019.

Six new alkaloids including four new chromeno[3,2-c]pyridines, diaporphasines A-D (1-4), and two new isoindolinones, meyeroguillines C and D (6-7), as well as three known compounds meyeroguilline A (5), 5-deoxybostrycoidin (8), and fusaristatin A (9), were isolated from an endophytic fungus Diaporthe phaseolorum SKS019. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Compounds 1-9 are alkaloid components reported for the first time from the Diaporthe sp., and diaporphasines A-D (1-4) are the third examples of alkaloids possessing the unique chromeno[3,2-c]pyridine nucleus. All isolated compounds 1-9 were evaluated for their cytotoxic activity in vitro using MDA-MB-435, HepG2, MCF10A, HCT116, and NCI-H460 human cell lines. Compound 8 exhibited cytotoxicity against MDA-MB-435 and NCI-H460 human cancer cell lines with IC50 values of 5.32 and 6.57µM, respectively, and compound 9 showed growth-inhibitory activity against MDA-MB-435 human cancer cell line with IC50 value of 8.15µM.

Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c.

One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 (9), and 1,2-dihydro-acetoxydehydroaustin B (10), were isolated from the mangrove endophytic fungus, Aspergillus sp. 16-5c. These structures were characterized by spectroscopic analysis, further the absolute configurations of stereogenic carbons for Compounds 1, 3, 4, 6, 7, 8, 9, and 10 were determined by single crystal X-ray diffraction analysis using Cu Kα radiation. Moreover, the absolute configurations of stereogenic carbons for Known Compounds 3, 7, 8, and 9 are identified here for the first time. Compounds 3, 7, and 8 showed acetylcholinesterase (AchE) inhibitory activity with IC50 values of 2.50, 0.40, and 3.00 µM, respectively.

Structural Characterization and Assessment of the Cytotoxicity of 2,3-Dihydro-1H-indene Derivatives and Coumarin Glucosides from the Bark of Streblus indicus.

A pair of enantiomers and a pair of 2,3-dihydro-1H-indene epimers, rac-indidene A (rac-1), indidenes B and C (2, 3); four new coumarin glucosides (4-7); and four known coumarin glucosides (8-11) were isolated from the bark of Streblus indicus (Bur.) Corner. The structures of 1-11 were defined by physical data analyses, including MS, NMR, and single-crystal X-ray diffraction. The absolute configurations of the 2,3-dihydro-1H-indene derivatives were defined via experimental and calculated ECD data. rac-Indidene A and indidenes B and C showed inhibitory activity against A549 and MCF-7 tumor cells with IC50 values in the range of 2.2 ± 0.1 to 7.2 ± 0.9 µM.

Polyketides with Immunosuppressive Activities from Mangrove Endophytic Fungus Penicillium sp. ZJ-SY2.

Nine polyketides, including two new benzophenone derivatives, peniphenone (1) and methyl peniphenone (2), along with seven known xanthones (3-9) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY2 isolated from the leaves of Sonneratia apetala. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Compounds 1, 3, 5, and 7 showed potent immunosuppressive activity with IC50 values ranging from 5.9 to 9.3 µg/mL.

Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity.

Four new polyketides: nectriacids A-C (1-3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher's ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC50 values of 23.5 and 42.3 µM, respectively, which were more potent than positive control (acarbose, IC50, 815.3 µM).

Asperlones A and B, dinaphthalenone derivatives from a mangrove endophytic fungus Aspergillus sp. 16-5C.

Racemic dinaphthalenone derivatives, (±)-asperlone A (1) and (±)-asperlone B (2), and two new azaphilones, 6'-hydroxy-(R)-mitorubrinic acid (3) and purpurquinone D (4), along with four known compounds, (-)-mitorubrinic acid (5), (-)-mitorubrin (6), purpurquinone A (7) and orsellinic acid (8), were isolated from the cultures of Aspergillus sp. 16-5C. The structures were elucidated using comprehensive spectroscopic methods, including 1D and 2D NMR spectra and the structures of 1 further confirmed by single-crystal X-ray diffraction analysis, while the absolute configuration of 3 and 4 were determined by comparing their optical rotation and CD with those of the literature, respectively. Compounds 1, 2 and 6 exhibited potent inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with IC50 values of 4.24 ± 0.41, 4.32 ± 0.60 and 3.99 ± 0.34 µM, respectively.

Cytotoxic metabolites from the mangrove endophytic fungus Aspergillus sp. GXNU QG1a.

A new benzoquinone, guxiumasperone A (1), and a new diisoprenyl-cyclohexene-type meroterpenoids, biscognienyne M (2), along with four known diisoprenyl-cyclohexene analogues was isolated from the mangrove endophytic fungus Aspergillus QG1a. Their structures were determined by extensive spectral analysis of 1D and 2D NMR, HR-ESI- MS, and X-ray crystallography. Compound 1 was deduced by a single-crystal X-ray diffraction analysis, and the absolute configuration of 2 was further unequivocally elucidated by comparing the experimental electronic circular dichroism (ECD) data with calculated ECD spectra. Compounds 1 and 2 showed significant cytotoxic activity against selected tumour cells. Particularly, compound 2 exhibited strong activity against A2780 cancer cells with an IC50 value of 6.8 µM.

Two new polyketone derivatives from the mangrove endophytic fungus Aspergillus sp. GXNU TH4b.

Two new polyketones, exserone B (1) and cytosporone F (2), along with three known metabolites, were isolated from the mangrove endophytic fungus Aspergillus TH4b. The structures of 1 and 2 were determined by detailed NMR, and MS spectroscopic data. The absolute configurations of 1 and 2 were determined by single crystal X-ray diffraction analysis and the combination of experimental ECD and computational ECD, respectively. Compounds 1-2 have strong inhibitory activity against citrus Psyllid (Diaphorina citri) with 95.4% and 93.7% lethal at 1000 mg/kg.

Diisoprenyl-cyclohexene-type meroterpenoids from a mangrove endophytic fungus Aspergillus sp. GXNU-Y65 and their anti-nonalcoholic steatohepatitis activity in AML12 cells.

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 µM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.

A new anti-acetylcholinesterase α-pyrone meroterpene, arigsugacin I, from mangrove endophytic fungus Penicillium sp. sk5GW1L of Kandelia candel.

Arigsugacin I (1), a new α-pyrone meroterpene, along with two known compounds, arigsugacins F (2) and territrem B (3), were isolated from the mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their structures were identified through mass spectrometry and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low-temperature (100 K) single crystal X-ray diffraction with Cu Kα radiation. The absolute configuration of compound 2 was first reported by using X-ray copper radiation. Compounds 1-3 showed inhibitory activities against acetylcholinesterase with IC50 values of 0.64 ± 0.08 µM, 0.37 ± 0.11 µM, and 7.03 ± 0.20 nM, respectively.

New dimeric members of the phomoxanthone family: phomolactonexanthones A, B and deacetylphomoxanthone C isolated from the fungus Phomopsis sp.

Three new phomoxanthone compounds, phomolactonexanthones A (1), B (2) and deacetylphomoxanthone C (3), along with five known phomoxanthones, including dicerandrol A (4), dicerandrol B (5), dicerandrol (6), deacetylphomoxanthone B (7) and penexanthone A (8), were isolated in the metabolites of the fungus Phomopsis sp. HNY29-2B, which was isolated from the mangrove plants. The structures of compounds 1-3 were established on the basis of spectroscopic analysis. All compounds were evaluated against four human cancer cell lines including human breast MDA-MB-435, human colon HCT-116, human lung Calu-3 and human liver Huh7 by MTT assay. The compounds 4, 5, 7 and 8 showed cytotoxic activities against tested cancer cell lines (IC50 < 10 µM).

A new lactone from mangrove endophytic fungus Aspergillus sp. GXNU-A9.

A new lactone, asperlactone A (1), and four known lactone derivatives 2-5 were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-A9. Their structures were elucidated based on high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) datum, extensive nuclear magnetic resonance (NMR) spectroscopic analysis, and comparison with literature data. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis, and the absolute configuration of 1 was established. Compounds 1-5 were evaluated for their anti-inflammatory activities against nitric oxide (NO) production, and compounds 1-5 showed moderate inhibitory activities with IC50 values ranging from 15.87 to 30.48 µM.

A new chromone derivative from an endophytic Aspergillus sp. GXNU-B1.

A new chromone derivative, aspergione A (1), along with seven known metabolites, was isolated from a mangrove endophytic fungus, Aspergillus sp. GXNU-B1, which was collected from mangrove Acanthus ilicifolius L. Their structures and the absolute configuration of 1 were elucidated based on the analysis of HR-ESI-MS, NMR, and ECD calculation. Compounds 1-8 were evaluated for their anti-inflammatory effects on the production of nitricoxide (NO). Compounds 1 and 8 have potent inhibitory effects against NO production in activated macrophages with IC50 values of 38.26 and 44.30 µM, respectively.

A new sulphur-containing metabolite from a mangrove endophytic fungus Aspergillus sp. GXNU-MA.

A new sulphur-containing metabolite, asperiguxidione A (1), was isolated from a mangrove endophytic fungus Aspergillus sp. GXNU-MA, and four known alkaloids 2-5, were isolated together from this strain. Their structures were determined by the com-bination of 1D and 2D NMR spectroscopy, HR-ESI-MS, and ECD analysis. Compounds 1 and 2 exhibited mediate activity against Staphylococcus aureus and Enterobacter aerogenes with equal MIC values of 12.5 µg/mL. Compound 3 reduced NO production in LPS-stimulated cells with an IC50 value of 13.329 ± 0.53 µg/mL in the anti-inflammatory assay.