Cytotoxic Polyphenols from a Sponge‐Associated Fungus Aspergillus versicolor Hmp‐48

A new dibenzo[1,4]dioxin 1 , and two new prenylated diphenyl ethers, 2 and 3 , together with six known compounds, 4 – 9 , were isolated from a sponge‐associated fungus Aspergillus versicolor Hmp‐F48 by bioactivity‐guided fractionation. Their structures were elucidated by 1D‐ and 2D‐NMR, and MS analyses. The compounds showed potent cell growth inhibitory activities against HL‐60 cell line.     

Two new benzofuran derivatives from the fungus Stereum sp. YMF1.1684

A basidiomycete fungus, Stereum sp. YMF1.1684, was studied for its ability to produce new compounds on nutrient-enriched cultivation media. One new benzofuran, 2-hydroxy-1-((S)-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-yl)propan-1-one, named as phenostereum A (1) and one novel dimer benzofuran, named as phenostereum B (2) were isolated from EtOAc extract of the culture broth of the fungus Stereum sp. YMF1.1684. The structures were elucidated using spectroscopic data from 1D, 2D NMR and HRESIMS experiments.     

Westalsan: A New Acetylcholine Esterase Inhibitor from the Endophytic Fungus Westerdykella nigra

A new cytochalasan alkaloid, westalsan ( 1 ), along with two known cytochalasan compounds, phomacin B ( 2 ) and 19-hydroxy-19,20-dihydrophomacin C ( 3 ), were isolated from the solid rice culture of Westerdykella nigra, a marine-derived endophytic fungus, isolated from the roots of mangrove Avicennia marina (Forssk.) Vierh. The structures of compounds 1 – 3 were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase activity was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC₅₀ 0.056±0.003 μM), followed by compound 1 (IC₅₀ 0.088±0.005 μM) and compound 2 (IC₅₀ 0.140±0.007 μM) compared to donepezil (IC₅₀ 0.035±0.002 μM). This was further confirmed by molecular docking experiment.     

Bergamotane Sesquiterpenes with Alpha‐Glucosidase Inhibitory Activity from the Plant Pathogenic Fungus Penicillium expansum

Two new bergamotane sesquiterpene lactones, named expansolides C and D ( 1 and 2 ), together with two known compounds expansolides A and B ( 3 and 4 ), were isolated from the plant pathogenic fungus Penicillium expansum ACCC37275. The structures of the new compounds were established by detailed analyses of the spectroscopic data, especially 1D‐, 2D‐NMR, and HR‐ESI‐MS. In an in vitro bioassay, the epimeric mixture of expansolides C and D ( 1 and 2 ) (in a ratio of 2:1 at the temprature of the bioassay) exhibited more potent α‐glucosidase inhibitory activity (IC₅₀ =0.50 ± 0.02 mm ) as compared with the positive control acarbose (IC₅₀ = 1.90 ± 0.05 mm ). To the best of our knowledge, it was the first report on the α‐glucosidase inhibitory activity of bergamotane sesquiterpenes.     

New styrylpyrones from the fungal endophyte Penicillium glabrum isolated from Punica granatum

The endophytic fungus Penicillium glabrum was isolated from pomegranate fruits (Punica granatum) collected in Uzbekistan. Extracts of the fungus grown on rice yielded two new styrylpyrones, namely 3-methyldesmethoxyyangonin (1) and 3-methylbisnoryangonin (2), together with four known metabolites. The structures of the isolated compounds were elucidated on the basis of comprehensive spectral analysis (1D and 2D NMR and MS).     

New Indole Diketopiperazine Alkaloids from Soft Coral-Associated Epiphytic Fungus Aspergillus versicolor CGF 9-1-2

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide ( 1 ) and (−)19-epi-sclerotiamide ( 2 ), along with 13 known analogs ( 3 – 15 ), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical ¹³C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3 , 6 , 8 , 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.     

Aspergetherins A-D,New Chlorinated Biphenyls with anti-MRSA Activity from the Marine Sponge Symbiotic Fungus Aspergillus terreus 164018

Aspergetherins A-D ( 1 – 4 ), four new chlorinated biphenyls, were isolated from the rice fermentation of a marine sponge symbiotic fungus Aspergillus terreus 164018, along with seven known biphenyl derivatives ( 5 – 11 ). The structures of four new compounds were determined by a comprehensive analysis of the spectroscopic data, including HR-ESI-MS and 2D NMR data. All 11 isolates were evaluated for their anti-bacterial activity against two strains of methicillin-resistant Staphylococcus aureus (MRSA). Among them, compounds 1 , 3 , 8 and 10 showed anti-MRSA activity with MIC values of 1.0–128 μg/mL. Preliminary structure-activity relationship analysis unveiled that both chlorinated substitution and esterification of 2-carboxylic acid could impact the antibacterial activity of biphenyls.     

Structural and Stereochemical Studies of Hydroxyanthraquinone Derivatives from the Endophytic Fungus Coniothyrium sp

Four known hydroxyanthraquinones ( 1–4 ) together with four new derivatives having a tetralone moiety, namely coniothyrinones A–D ( 5–8 ), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C ( 7 ) as well. Coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium. Chirality 25:141–148, 2013. © 2012 Wiley Periodicals, Inc.     

New Spirostane from a Fungus Neohelicomyces hyalosporus and Its Bioactivity

A new spirostane, namely neohelicomyine B ( 1 ), together with six known steroids ( 2 – 7 ) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1 – 7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC₅₀ value of 8.4±2.1 μM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC₅₀ value of 3.0±0.2 μM.     

Azaphilones and Meroterpenoids from the Soft Coral-Derived Fungus Penicillium glabrum glmu003

Two new azaphilone compounds, daldinins G ( 1 ) and H ( 2 ), together with nine known compounds daldinin D ( 3 ), sargassopenilline B ( 4 ), austalide V ( 5 ), austalide K ( 6 ), austalide P ( 7 ), austalide P acid ( 8 ), austalide H ( 9 ), 13-O-deacetyaustalide I ( 10 ), and 17-O-demethylaustalide B ( 11 ), were isolated from the soft coral-derived fungus Penicillium glabrum glmu003. The new structures of 1 and 2 were elucidated on the basis of 1D and 2D NMR, mass spectra, and electronic circular dichroism (ECD) data analysis. Compound 5 showed weak inhibitory activity against pancreatic lipase (PL) with IC₅₀ value of 23.9 μg/mL.     

Enantiomeric Polyketides from the Starfish‐Derived Symbiotic Fungus Penicillium sp. GGF16‐1‐2

One new racemic mixture, penicilliode A ( 1 ) and four pairs of enantiomeric polyketides, penicilliode B and C ( 2 and 3 ) and coniochaetone B and C ( 4 and 5 ), were obtained from the starfish‐derived symbiotic fungus Penicillium sp. GGF16‐1‐2. Interestingly, the strain GGF16‐1‐2 can produce enantiomers. The absolute configuration of 1 was determined by X‐ray diffraction (XRD) analysis, and the absolute configurations of 2 – 4 were determined by the optical rotation (OR) values and electronic circular dichroism (ECD) calculations. Compounds 1 – 5 were firstly isolated from the marine‐derived fungus Penicillium as racemates, and 2 – 5 were separated by HPLC with a chiral stationary phase. All the compounds were evaluated for their antibacterial, cytotoxic and inhibitory activities against PDE4D2.     

New Indole Diketopiperazine Alkaloids from Soft Coral‐Associated Epiphytic Fungus Aspergillus sp. EGF 15‐0‐3

Three new indole diketopiperazine alkaloids, 11‐methylneoechinulin E and variecolorin M, and (+)‐variecolorin G, along with 12 known analogs, were isolated from a soft coral‐associated epiphytic fungus Aspergillus sp. EGF 15‐0‐3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HR‐ESI‐MS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of (+)‐ and (?)‐variecolorin G were determined by experimental and quantum‐chemical ECD investigations and single‐crystal X‐ray diffraction analysis. Variecolorin G is a pair of enantiomeric mixtures with a ratio of 1 : 2. Moreover, (+)‐neoechinulin A is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI‐H1975 gefitinib resistance (NCI‐H1975/GR) cell lines were preliminarily evaluated by MTT method.     

O-Heterocyclic Embeurekols from Embellisia eureka,an Endophyte of Cladanthus arabicus

Three new polyketides (-)-1 , (+)-1 , and 2 ) were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of (-)-1 , (+)-1 , and 2 were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD analysis, and the modified Mosher method. Chirality 25:250–256, 2013. © 2013 Wiley Periodicals, Inc.     

Chaetochromones A – C,Three New Polyketides from Mangrove Plant Derived Endophytic Fungus Phomopsis sp. SCSIO 41006

Three new polyketides, chaetochromones A – C ( 1  –  3 ), together with a chromone ( 4 ), were isolated from the ethyl acetate extract of mangrove‐derived fungus Phomopsis sp. SCSIO 41006. Their structures were elucidated by means of spectroscopic techniques (UV, IR, MS, 1D‐ and 2D‐NMR). The absolute configurations of the new compounds were established by CD data.     

New Polyketide and Sesquiterpenoid Derivatives from the Magellan Seamount-Derived Fungus Penicillium rubens AS-130

Rubenpolyketone A ( 1 ), a polyketide featuring a new carbon skeleton having cyclohexenone condensed with a methyl octenone chain and a new linear sesquiterpenoid, chermesiterpenoid D ( 2 ), together with seven known secondary metabolites ( 3 – 9 ) were isolated and identified from the Magellan Seamount-derived fungus Penicillium rubens AS-130. Their structures were determined based on detailed analysis of NMR and mass spectroscopic data and the absolute configurations of these two new compounds were elucidated by the combination of quantum mechanical (QM)-NMR and time-dependent density functional (TDDFT) ECD calculation approaches. Chermesiterpenoids B ( 3 ) and C ( 4 ) showed potent inhibitory activities against the aquatic pathogen Vibrio anguillarum with MIC values of 0.5 and 1 μg/mL, respectively, while chermesin F ( 6 ) exhibited activity against Escherichia coli with MIC value of 1 μg/mL.     

Phialomyces macrosporus: Chemical Constituents,Antimicrobial Activity and Complete NMR Assignments for the 7,7′‐Biphyscion

Five known secondary metabolites, chrysophanol ( 1 ), 7,7′‐biphyscion ( 2 ), secalonic acid D ( 3 ), mannitol ( 4 ) and trehalose ( 5 ) were isolated for the first time from the extracts of the fungus Phialomyces macrosporus. Their structures were elucidated by NMR methods (1D and 2D NMR analysis), optical activity and ESI‐MS. Complete ¹H and ¹³C assignments were performed for compound 2 . The antimicrobial activity was evaluated by serial microdilution assay for compounds 2 and 3 and results showed that compound 3 exhibited a significant growth inhibition at concentrations of 15.6 mg/ml (S. aureus and S. choleraesius) and 0.97 mg/mL (B. subtilis), comparable to the positive control.     

Two New Phenol Derivatives from the Cold Seep-Derived Fungus Aspergillus insuetus SD-512

Two new phenol derivatives, namely insphenol A ( 1 ) and acetylpeniciphenol ( 2 ), along with seven known analogs ( 3 – 9 ), were isolated from the deep-sea cold seep-derived fungus, Aspergillus insuetus SD-512. The structures of 1 and 2 were established by extensive interpretation of NMR and mass spectroscopic data. The absolute configuration of 1 was determined by the combination of coupling constant analysis and acid hydrolysis. Among the isolated compounds, insphenol A ( 1 ) represents the first example of isopentenyl phenol derivative with a unique 1-glycosylation from the species Aspergillus insuetus. The isolated new compounds were evaluated for antibacterial activities against six human or aquatic pathogens, while compound 2 exhibited inhibitory effect against Edwardsiella tarda, Vibrio alginolyticus, and V. vulnificus, with MIC values of 4, 8, and 8 μg/mL, respectively.     

Phenolic metabolites from Pyruscalleryana and evaluation of its free radical scavenging activity

Investigation of the aqueous alcoholic extract of Pyruscalleryana Decne. leaves led to the isolation of two new phenolic acids glycosides, namely protocatechuoylcalleryanin-3-O-β-glucopyranoside (1) and 3′-hydroxybenzyl-4-hydroxybenzoate-4′-O-β-glucopyranoside (2), together with nine known compounds among them lanceoloside A and methylgallate, which have been isolated for the first time from the genus Pyrus. Structures of the isolated compounds were established by spectroscopic analysis, including UV, IR, HRESI-MS, and 1D/2D NMR. The total extract and some isolated compounds were determined against DPPH (2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazinyl radical, for their free radical scavenging activity, the total alcoholic extract showed strong antioxidant activity while the two new compounds showed weak antioxidant activity.     

蛇足石杉中的新内生真菌及其代谢产物的分离与鉴定

从蛇足石杉内生菌的次级代谢产物中寻找活性成分,为进一步开发利用蛇足石杉药用植物资源提供了新途径,但至今其内生菌代谢产物的系统性研究较为少见。种类丰富的内生真菌普遍存在于各种植物中,但蕨类植物中内生真菌的研究较少。为了寻找蛇足石杉内生菌中的细胞毒活性成分,该研究从蛇足石杉根部分离得到一株球毛壳属(Chaetomium sp.)真菌M336,对其化学成分进行了研究。对蛇足石杉内生真菌M336采用PDA固体培养基扩大发酵,发酵物经提取及乙酸乙酯萃取后,通过正相硅胶柱色谱法、Sephadex LH-20凝胶柱色谱法、薄层制备、高效液相色谱等色谱手段对其发酵物中的化学成分进行分离纯化,利用理化性质、质谱、核磁等波谱分析技术,并结合相关文献数据鉴定化合物的结构。结果表明：从内生真菌M336发酵提取物的乙酸乙酯萃取部分分离并鉴定出8个化合物,分别为chaetoviridines F、chaetoviridines E、5′-epichaetoviridin A、5′-epichaetoviridin A、xanthoquinodins Al、xanthoquinodins A2、xanthoquinodins B1和毛壳菌素。从M336中分离得到8个化合物,化合物3有一定的抑菌作用,其余化合物有一定的细胞毒活性。该研究结果丰富了蛇足石杉内生真菌球毛壳属中的天然细胞毒活性的化合物。     

Novel Flavones from the Root of Phytolacca acinosa Roxb.

Two new flavones, 6,7‐methylenedioxy‐4‐hydroxypeltogynan‐7′‐one ( 1 ), cochliophilin B ( 2 ), as well as two known ones, cochliophilin A ( 3 ) and 6‐methoxy‐7‐hydroxy flavone ( 4 ), were isolated from the ethanol extract of the root of Phytolacca acinosa Roxb . Compound 1 is a flavanol framework with one δ‐lactone unit, which is rather rare in nature. The structures of the new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D‐ and 2D‐NMR) analyses, the absolute configuration of 1 was established by comparing experimental and calculated electronic circular dichroism spectra. The structures of known compounds were fixed by comparison with literatures data. Compounds 2 and 4 showed modest inhibitory activities against BEL‐7402 cell line, with IC₅₀ values of 28.22 and 39.16 μmol/L, respectively.