Phytotoxic Metabolites Isolated from Aspergillus sp., an Endophytic Fungus of Crassula arborescens

Aspergillus sp., an endophytic fungus isolated from Crassula arborescens, displayed potent inhibitory activity against the seed germination of Arabidopsis thaliana. The bioactivity-guided fractionation of the culture extract of Aspergillus sp. MJ01 led to the isolation of nine compounds, including one previously undescribed furanone, namely aspertamarinoic acid (1), and eight known compounds, (−)-dihydrocanadensolide (2), kojic acid (3), citreoisocoumarin (4), astellolide A (5), astellolide B (6), astellolide G (7), cyclo-N-methylphenylalanyltryptophenyl (8) and (−)-ditryptophenaline (9). In the evaluation of the phytotoxic activities of compounds 1–9, the results suggested that 1 and 5 showed significant inhibitory activity on the seed germination of A. thaliana. This is the first report to disclose the phytotoxic activity of these compounds.     

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.     

Two New Meroterpenes from the Mangrove Endophytic Fungus Aspergillus sp. 085241B

Two new meroterpenes, ‘acetoxydehydroaustin B’ ( 1 ) and ‘1,2‐dihydro‐acetoxydehydroaustin B’ ( 2 ) were isolated in the form of a mixed crystal from the mangrove endophytic fungus Aspergillus sp. 085241B. Their structures and absolute configurations were determined by extensive analysis of their spectra and X‐ray diffraction data. In a preliminary bioassay, the mixed crystal did not exhibit activities against cancer cell lines of MDA‐MB‐435, SKBR3, HepG2, HEP3B, PC‐3, and A549, as well as against α‐glucosidase and tyrosinase.     

Benzodiazepine Alkaloids from Marine‐Derived Endophytic Fungus Aspergillus ochraceus

A new fungus‐derived benzodiazepine analogue, 2‐hydroxycircumdatin C ( 1 ), and a compound which has been isolated from a natural resource for the first time, but has been previously synthesized, namely (11aS)‐2,3‐dihydro‐7‐methoxy‐1H‐pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11(10H,11aH)‐dione ( 2 ), along with five structurally related known alkaloids ( 3 – 7 ), were isolated from Aspergillus ochraceus, an endophytic fungus derived from the marine brown alga Sargassum kjellmanianum. Their structures were established on the basis of spectroscopic methods. The absolute configuration of 1 was determined through CD evidence. Compound 1 displayed significant DPPH radical‐scavenging activity with an IC₅₀ value of 9.9 μM , which is 8.9‐fold more potent than that of butylated hydroxytoluene (BHT), a well‐known synthetic positive control.     

Two New Cyclic Pentapeptides from the Marine‐Derived Fungus Aspergillus versicolor

Two new cyclic pentapeptides, named versicotides A ( 1 ) and B ( 2 ), were obtained from a marine‐derived fungus strain ZLN‐60, identified as Aspergillus versicolor. Their structures were established on the basis of chemical and spectroscopic evidence. Versicotides are new cyclic pentapeptides which contain an L ‐alanine residue, two anthranilic acid (=2‐aminobenzoic acid) residues, and two N‐methyl‐L ‐alanine residues. Antitumor activities were evaluated by the SRB and MTT methods.     

Pentacyclic Cytochalasins and Their Derivatives from the Endophytic Fungus Phomopsis sp. xz-18

Eight new cytochalasins 1–8 and ten known analogs 9–18 were isolated from the endophytic fungus Phomopsis sp. xz-18. The planar structures of the cytochalasins were determined by HR-ESI-MS and NMR analysis. Compounds 1, 2, 9 and 10 were 5/6/6/7/5-fused pentacyclic cytochalasins; compounds 3 and 4 had conjugated diene structures in the macrocycle; and compound 6 had a β,γ-unsaturated ketone. The absolute configuration of 6 was confirmed for the first time by the octant rule. The acid-free purification process proved that the pentacyclic system was a natural biosynthetic product and not an acid-mediated intramolecular cyclized artifact. The new compounds did not exhibit activities against human cancer cell lines in cytotoxicity bioassays or antipathogenic fungal activity, but compounds 1, 3 and 4 showed moderate antibacterial activity in disk diffusion assays.     

A novel cyclic dipeptide from deep marine-derived fungus Aspergillus sp. SCSIOW2

A novel cyclic dipeptide, 14-hydroxy-cyclopeptine (1), was purified from a deep sea derived fungal isolate identified as an Aspergillus sp. The structure was elucidated by detailed spectroscopic analyses using 1D and 2D NMR experiments and high resolution mass spectrometry. The absolute configuration of the amino acid was determined by Marfey's method. Two conformational isomers of 1 were established by ROE analyses. 1 inhibited nitric oxide production with IC₅₀ values at 40.3 μg/mL in a lipopolysaccharide and recombinant mouse interferon-γ -activated macrophage-like cell line, RAW 264.7 and showed no cytotoxic effect in the tested dose range up to 100 μg/mL.     

来源湛江红树内生真菌的二氢异香豆素及其抑菌活性

为了研究湛江红树(Rhizophora apiculata)植物内生真菌Fusarium sp.F67和B42的二氢异香豆素类次级代谢产物及其抑菌活性,采用色谱技术对菌株F67和B42的代谢产物进行分离纯化,确认所得化合物的结构为:3,6,8-三羟基-3,4,5,7-四甲基-3,4-二氢异香豆素(sclerotinin A)(1),二氢橘霉素(2)、5-甲基蜂蜜曲菌素(3)、5-羧基蜂蜜曲菌素(4)、4-羟基蜂蜜曲菌素(5)和蜂蜜曲菌素(6),并利用滤纸片琼脂扩散法检测化合物对7种常见致病菌的抑菌活性。在1.0 g/L质量浓度下化合物1~4对受试菌株的抑菌圈范围为5.1~11.0 mm,其中化合物4的抑菌活性相对较强,抑菌谱相对较广,可为挖掘新型抗菌药物的研究提供补充。     

从红树林内源真菌2526#分离到Sterigmatocystin

从海洋资源中寻找药物已越来越受到重视 ,已有的研究表明海洋资源有可能成为治疗人类疑难病症和延年益寿药物的丰富源泉[1] 。本研究组在从海洋微生物筛选新药的过程中 ,已发现多种结构奇特而具有强生理活性的化合物[2～ 4 ] 。Ｓｔｅｒｉｇｍａｔｏｃｙｓｔｉｎ最早分离自陆生真菌Ａｓｐｅｒｇｉｌｌｕｓｖｅｒｓｉｃｏｌｏｒ的代谢产物[5] ,随后人们对其结构、生源合成及药理活性进行了广泛的研究。结果表明 ,ｓｔｅｒｉｇｍａｔｏｃｙｓｔｉｎ是细胞毒性更强的化合物ＡｆｌａｔｏｘｉｎＢ1的生源合成前体。本文报道从采自香港红树Ａｖｉ…     

Two New Secoanthraquinone Derivatives from the Marine‐Derived Endophytic Fungus Aspergillus wentii EN‐48

Two new secoanthraquinone derivatives, wentiquinones A ( 1 ) and B ( 2 ), together with the eight known compounds 3 – 10 , were isolated from the culture extracts of Aspergillus wentii EN‐48, an endophytic fungus derived from an unidentified marine brown algal species of the genus Sargassum. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis.     

Two Antimicrobial Heterodimeric Tetrahydroxanthones with a 7,7′-Linkage from Mangrove Endophytic Fungus Aspergillus flavus QQYZ

Mangrove endophytic fungi represent significant and sustainable sources of novel metabolites with unique structures and excellent biological activities, attracting extensive chemical investigations. In this research, two novel heterodimeric tetrahydroxanthones, aflaxanthones A (1) and B (2), dimerized via an unprecedented 7,7′-linkage, a sp³-sp³ dimeric manner, were isolated from the mangrove endophytic fungus Aspergillus flavus QQYZ. Their structures were elucidated through high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopy, the absolute configurations of them were determined by a single-crystal X-ray diffraction combined with calculated electronic circular dichroism (ECD) spectra and a 1D potential energy scan. These compounds were evaluated for antifungal activities in vitro and exhibited broad-spectrum and potential antifungal activities against several pathogenic fungi with minimum inhibitory concentration (MIC) values in the range of 3.13–50 μM. They also performed moderate antibacterial activities against several bacteria with MIC values in the range of 12.5–25 μM. This research enriched the resources of lead compounds and templates for marine-derived antimicrobial drugs.     

Diketopiperazine Alkaloids Produced by the Endophytic Fungus Aspergillus fumigatus from the Stem of Erythrophloeum fordii Oliv.

Four new diketopiperazine alkaloids, rel‐(8R)‐9‐hydroxy‐8‐methoxy‐18‐epi‐fumitremorgin C ( 1 ), rel‐(8S)‐19,20‐dihydro‐9,20‐dihydroxy‐8‐methoxy‐9,18‐di‐epi‐fumitremorgin C ( 2 ), rel‐(8S,19S)‐19,20‐dihydro‐9,19,20‐trihydroxy‐8‐methoxy‐9‐epi‐fumitremorgin C ( 3 ), and (3S,8S,9S,18S)‐8,9‐dihydroxyspirotryprostatin A ( 4 ), together with the eight known compounds 5 – 12 , were isolated from the endophytic fungus Aspergillus fumigatus. The structures of the new compounds were determined by extensive spectroscopic methods including HR‐ESI‐MS, NMR, and CD experiments. Compound 12 showed weak inhibitory activity in vitro against the release of β‐glucuronidase in rat polymorphonuclear leukocytes induced by the platelet‐activating factor. None of the twelve compounds exhibited detectable cytotoxic activities toward five human tumor cell lines (HCT‐8, Bel‐7402, BGC‐823, A549, and A2780) in the MTT assay.     

培养南海红树林内源真菌Fusarium sp. ZZF60产新型蒽醌衍生物

通过人工发酵培养,从南海红树林内源真菌Fusarium sp.ZZF60的培养液中分离得到:1种新蒽醌衍生物,6,8-二甲氧基-1-甲基-2-(3-氧丁基)蒽醌(1),以及5种已知化合物:7-羟基-3-(4-甲氧基苯基)苯并-γ-吡喃酮(2),2,4-二羟基-6-[(1′E,3′E)-1′,3′-戊二烯基]苯甲醛(3),(E)-4-羟基肉桂酸甲酯(4),4-(4-羟基苯基)-2-丁醇(5),4-羟基苯甲酸(6)。它们的结构通过MS、NMR等波谱分析推导确定。初步药理活性显示,化合物1抑制体外培养人喉癌细胞Hep2和人肝癌细胞HepG2的IC50分别为16和23μmol/L。     

New Helvolic Acid Derivatives with Antibacterial Activities from Sarocladium oryzae DX-THL3, an Endophytic Fungus from Dongxiang Wild Rice (Oryza rufipogon Griff.)

Three new helvolic acid derivatives (named sarocladilactone A (1), sarocladilactone B (2) and sarocladic acid A (3a)), together with five known compounds (6,16-diacetoxy-25-hy- droxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (3b), helvolic acid (4), helvolinic acid (5), 6-desacetoxy-helvolic acid (6) and 1,2-dihydrohelvolic acid (7)), were isolated from the endophytic fungus DX-THL3, obtained from the leaf of Dongxiang wild rice (Oryza rufipogon Griff.). The structures of the new compounds were elucidated via HR-MS, extensive 1D and 2D NMR analysis and comparison with reported data. Compounds 1, 2, 4, 5, 6 and 7 exhibited potent antibacterial activities. In particular, sarocladilactone B (2), helvolinic acid (5) and 6-desacetoxy-helvolic acid (6) exhibited strongly Staphylococcus aureus inhibitory activity with minimum inhibitory concentration (MIC) values of 4, 1 and 4 μg/mL, respectively. The structure–activity relationship (SAR) of these compounds was primarily summarized.     

Pestalotiopisorin B,a new isocoumarin derivative from the mangrove endophytic fungus Pestalotiopsis sp. HHL101

Abstract

A new isocoumarin derivative pestalotiopisorin B (1), along with six known compounds, (R)-(-)- mellein methyl ether (2), pestalotiopyrone G (3), (R)-mevalonolactone (4), pestalotiollides A–B (5–6) and pestalotiopsol A(7) were isolated from Pestalotiopsis sp., an endophytic fungus obtained from Chinese mangrove plant Rhizophora stylosa. Their structures were elucidated unambiguously by the comprehensive analysis of extensive spectroscopic data. Compound 1 exhibited modest antibacterial activity against Escherichia coli and Pseudomonas aeruginosa with 12.5?μg/ml, 50?μg/ml, respectively. Compound 4 showed moderate calcineurin inhibitory activity towards p-nitrophenyl phosphate (IC₅₀ =134.29?±?5.377?μM).     

Cytotoxic compounds from the marine-derived fungus Aspergillus sp. recovered from the sediments of the Brazilian coast

A fungal strain of Aspergillus sp. (BRF 030) was isolated from the sediments collected in the northeast coast of Brazil, and the cytotoxic activity of its secondary metabolites was investigated against HCT-116 tumour cell line. The cytotoxicity-guided fractionation of the extracts from this fungus cultured in potato-dextrose-sea water for 14 days at room temperature yielded the hetero-spirocyclic γ-lactams pseurotin A (1), pseurotin D (2) and pseurotin FD-838 (7), the alkaloids fumitremorgin C (5), 12,13-dihydroxy fumitremorgin C (6), methylsulochrin (4) and bis(dethio)bis(methylthio)gliotoxin (3). Among them, fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6) were the most active. The cytotoxic activities of the extracts from Aspergillus sp. grown from 7 to 28 days were investigated, and they were associated with the kinetic production of the compounds. The most active extracts (14 and 21 days) were those with the highest relative concentrations of the compounds fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6).     

Meroterpenoids and Steroids from the Marine-Derived Fungus Trametes sp. ZYX-Z-16

Marine fungi can metabolize structurally diverse active components, and have become an important source of drug lead molecules. In the present study, the chemical investigation on the EtOAc extract of the fermentation broth of the marine-derived fungus Trametes sp. ZYX-Z-16 led to the isolation of eight meroterpenoids (1–8), including two undescribed ones, together with ten ergostane steroid analogues (9–18). The structures of two new spiromeroterpenoids, asnovolin H (1) and asnovolin I (2), were determined based on 1D, 2D NMR, and HRESIMS spectroscopic data along with ECD spectra calculations. All compounds were tested for antibacterial and α-glucosidase inhibitory activity. Among them, compound 12 showed definite antibacterial activities against Staphylococcus aureus ATCC 6538 (MIC 32 μg/mL) and Bacillus subtilis ATCC 6633 (MIC 16 μg/mL). In addition, compounds 9 and 10 showed superior inhibitory activity, with IC₅₀ values of 104.1 and 111.3 μM, respectively, to the positive control acarbose (304.6 μM).     

Two new tricycloalternarenes from Hawaiian endophytic fungus Didymella sp. FT433

Two new compounds, tricycloalterenes M and N (1 and 2) and six known analogs were isolated from the cultured broth of Didymella sp. FT433. The structures of all the compounds were elucidated through the analysis of HRMS and NMR spectroscopic data. The absolute configurations (AC) of the new compounds were determined by CD. All compounds were tested against A2780 and cisplatin resistant A2780 (A2780CisR) cell lines, and pathogenic bacteria Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa, but none was active.     

Furanone Derivatives from Aspergillus sp. XW‐12, an Endophytic Fungus in Huperzia serrata

Two new 5‐methoxyfuran‐3(2H)‐one derivatives, huaspenone A ( 1 ) and B ( 2 ), together with four known ones, i.e., aspertetronin A ( 3 ), aspertetronin B ( 4 ), gregatin E ( 5 ), and penicilliol A ( 6 ), were isolated from the cultures of an endophytic fungus Aspergillus sp. XW‐12, derived from the stems of Huperzia serrata. The structures of the new isolates were established by detailed interpretation of the 1D‐ and 2D‐NMR and HR‐ESI‐MS data.     

Research Advances of Bioactive Sesquiterpenoids Isolated from Marine-Derived Aspergillus sp.

Marine fungi Aspergillus sp. is an important source of natural active lead compounds with biological and chemical diversity, of which sesquiterpenoids are an extremely important class of bioactive secondary metabolites. In this paper, we review the sources, chemical structures, bioactivity, biosynthesis, and druggability evaluation of sesquiterpenoids discovered from marine fungi Aspergillus sp. since 2008. The Aspergillus species involved include mainly Aspergillus fumigatus, Aspergillus versicolor, Aspergillus flavus, Aspergillus ustus, Aspergillus sydowii, and so on, which originate from sponges, marine sediments, algae, mangroves, and corals. In recent years, 268 sesquiterpenoids were isolated from secondary metabolites of marine Aspergillus sp., 131 of which displayed bioactivities such as antitumor, antimicrobial, anti-inflammatory, and enzyme inhibitory activity. Furthermore, the main types of active sesquiterpenoids are bisabolanes, followed by drimanes, nitrobenzoyl, etc. Therefore, these novel sesquiterpenoids will provide a large number of potential lead compounds for the development of marine drugs.