Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae

Two new compounds, lasdiplactone (1) and lasdiploic acid (2) and one known compound 3 were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structures of new compounds were determined by interplay of spectral techniques (IR, mass, ¹H NMR, ¹³C NMR, DEPT, and 2D NMR). The absolute configuration at C-4 position of 1 was established as S using a process similar to modified Mosher’s method. The absolute configuration of 2 was established by comparing its ECD spectrum with the calculated ECD spectra of all possible isomers. In the in vitro XO inhibition assay, the highest inhibition was exhibited by 3 with an IC₅₀ of 0.38 ± 0.13 μg/ml, followed by 2 with an IC₅₀ of 0.41 ± 0.1 μg/ml and the least in 1. The oxidized form of 1 also showed high XO inhibition with IC₅₀ of 0.35 ± 0.13 μg/ml.     

Isolation of taxol producing endophytic fungus Alternaria brassicicola from non-Taxus medicinal plant Terminalia arjuna

World Journal of Microbiology and Biotechnology - Shigella type III effector OspF, a nuclear translocation protein, has been showed to have an essential role in Shigella flexneri infection and...     

Antifungal activity of altenusin isolated from the endophytic fungus Alternaria sp. against the pathogenic fungus Paracoccidioides brasiliensis

BackgroundAltenusin is a biphenyl derivative isolated from different species of fungi, which presents several biological activities.AimsWe report the antifungal activity of the altenusin isolated from the endophytic fungus Alternaria sp., against clinical isolates of Paracoccidioides brasiliensis, and its action on cell walls of P. brasiliensis and the nonpathogenic yeast Schizosaccharomyces pombe.MethodsIn vitro antifungal activity of altenusin was evaluated using the broth microdilution method against 11 strains of P. brasiliensis and one strain of S. pombe. The effects of the altenusin on the cell wall were estimated using the sorbitol protection assay.ResultsThe altenusin presented strong activity against P. brasiliensis with MIC values ranging between 1.9 and 31.2 μg/ml, and 62.5 μg/ml for S. pombe. Our results demonstrated that the MIC values for altenusin were increased for P. brasiliensis Pb18 and for S. pombe when the medium was supplemented with sorbitol. Additionally, S. pombe cells treated with altenusin were more rounded in shape than untreated cells.ConclusionsAltenusin showed activity against clinical strains of P. brasiliensis at the concentration tested, and this compound probably affects fungal cell walls. These findings suggest that altenusin could act through the inhibition of cell wall synthesis or assembly in P. brasiliensis and S. pombe, and could be considered as a lead compound for the design of new antifungals.     

Chemistry and weak antimicrobial activities of phomopsins produced by mangrove endophytic fungus Phomopsis sp. ZSU-H76

Three metabolites named phomopsin A (1), B (2) and C (3), together with two known compounds cytosporone B (4) and C (5), were isolated from the mangrove endophytic fungus, Phomopsis sp. ZSU-H76 obtained from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly by 1D and 2D NMR spectroscopic techniques. The medium-sized cyclic phenol ether based on 1 or 2 is rare in natural products. In bioassays, compounds 1, 2, and 3 had no significant antibiotic activities, but compounds 4 and 5 inhibited two fungi Candida albicans and Fusarium oxysporum with an MIC ranging from 32 to 64 microg/ml.     

Natural products of Alternaria sp., an endophytic fungus isolated from Salvadora persica from Saudi Arabia

This study is to evaluate the potential of endophytic fungi of Salvadora persica for the production of bioactive compounds against pathogenic bacteria and fungi. Forty-two fungal isolates were obtained from 135 young and old stem and 125 root segments. Those 42 isolates representing ten fungi include: Trichoderma sp. (the most common), two species of Alternaria, Rhizopus arrhizus and 6 sterile mycelia. The ten fungi were grown in liquid culture and their crude extracts were tested against pathogenic bacteria and fungi. Nine crude extracts gave positive reactions against pathogenic bacteria of which Alternaria sp. (A8) was chosen further study. The fungal isolate was growing as sterile mycelium and was identified by phylogenetic analyses based on LSU rDNA sequence data and it might represent undescribed species of Alternaria. Sixty-two bioactive chemical compounds were identified from the ethyl acetate crude extracts of Alternaria sp., of which the following were recorded as major compounds in the active sub-fractions. These compounds showed strong antibacterial activity in combination.     

Bioactive metabolites from Alternaria brassicicola ML-P08, an endophytic fungus residing in Malus halliana

A total of 48 strains were isolated from the normal tissues of Malus halliana and the EtOAc extracts of their cultures were subjected to primary antimicrobial screening against four test bacteria and three fungi. As a result, 22 strains exhibited antimicrobial activity against at least one test microbe. Among them, Alternaria brassicicola ML-P08 showing strong activity (MICs: 0.31–2.50 mg/ml) was selected for further investigation on its secondary metabolites. Bioassay-guided fractionation of the EtOAc extract of its liquid culture afforded seven compounds, which were identified as alternariol (1), alternariol 9-methyl ether (2), altechromone A (3), herbarin A (4), cerevisterol (5), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6) and 3β-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one (7), respectively, by spectral means (MS, IR, ¹H- and ¹³C-NMR). In vitro antimicrobial assay showed that compound 3 was substantially active against Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Candida albicans with the MICs of 3.9, 3.9, 1.8, and 3.9 μg/ml, respectively. Compound 4 also showed pronounced antifungal activity against Trichophyton rubrum and C. albicans with MICs of both 15.6 μg/ml. In addition, compound 1 exhibited strong xanthine oxidase inhibitory activity with the IC₅₀ of 15.5 μM, comparable to that of positive control, allopurinol (IC₅₀: 10.7 μM).     

Paeonol produced by Chaetomium sp., an endophytic fungus isolated from Paeonia suffruticosa

In order to research the relationship between endophytic fungus and active ingredients in medicinal Paeonia suffruticosa, a total of 57 fungal isolates were isolated from the roots, stems, leaves and buds of medicinal plant Paeonia ostii; mycelium was collected after these fungal isolates were fermented on PDA medium for a few days; then the mycelium products were extracted; their extracts were analyzed by gas chromatography–mass spectrometry. With this method, a strain endophytic fungi named J1-2 which can produce paeonol was screened. Paeonol produced by J1-2 was analyzed by using a high resolution mass spectrometer (HRMS) and nuclear magnetic resonance (NMR). The potential paeonol-procucing named J1-2 was identified Chaetomium based on morphological characteristics and ITS sequence analysis. The current research initially indicates that endophytic fungi can affect the potency of peony. At the same time it also indicates that the numerous endophytic fungi inside the medicinal Paeonia suffruticosa are precious resource for the pharmaceutical natural products that are originally from the Paeonia suffruticosa.     

Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp., inhibits trypanothione reductase from Trypanosoma cruzi

Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiological agents of several diseases in tropical areas of the world, for which there is an urgent need for effective and affordable treatment. In this regard, we are screening the Brazilian biodiversity, especially its flora and mycota, for natural products that could serve as leads for drug development against these diseases. Trypanothione reductase (TR) is an enzyme involved in the protection of Trypanosoma and Leishmania species against oxidative stress, and is considered to be a validated drug target. The endophytic fungus Alternaria sp. (UFMGCB55) was isolated from the plant Trixis vauthieri DC (Asteraceae), known to contain trypanocidal compounds. The organic extract of the culture of Alternaria sp. was able to inhibit TR by 99%, when tested at 20 microg mL(-1). Fractionation of the extract identified altenusin, a biphenyl derivative with an IC50 value of 4.3+/-0.3 microM in the TR assay. This compound is the first in its class to have shown TR inhibitory activity, opening new perspectives for the design of more effective derivatives that could serve as drug leads for new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis.     

Optimization of protease production by endophytic fungus,Alternaria alternata,isolated from an Australian native plant

Endophytes are recognised as potential sources of novel secondary metabolites, including enzymes and drugs, with applications in medicine, agriculture and industry. There is a growing need for new enzymes, including proteases, for use in industry that can function under a variety of conditions. In this study, three fungal endophytes (Alternaria alternata, Phoma herbarum and an unclassified fungus), were isolated from the Australian native plant, Eremophilia longifolia, and assessed for production of proteases. The lyophilised growth media obtained after fungal fermentation were analysed for protease production using enzyme activity assays. Protease production was optimised by assessing the effects of temperature, pH, carbon source and nitrogen source on activity. A. alternata showed the greatest protease activity in a wide range of pH (3–9). The broadest activity between 9 and 50 °C was observed at pH 7, suggesting a neutral protease. Overall, the optimum conditions were 37 °C and pH 7 with a maximum specific activity value of 69.86 BAEE units/mg. The characteristics demonstrated by this fungal endophyte showed that it is a potential source of an enzyme with particular application in the dairy industry. However, further studies of the tolerance to higher temperatures and pH will indicate whether the enzyme is suitable to such applications.     

Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2

Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1–4), three new natural products, 6-methoxycarbonyl-2′-methyl-3,5,4′,6′-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2′-rnethyl-3,5,4′,6′-tetramethoxy-diphenyl ether (6), and 2-chlor-4′-hydroxy-6-methoxy carbonyl-2′-methyl-3,5,6′-trimethoxy-diphenyl ether (7), and eleven known compounds (8–18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh₂(OCOCF₃)₄-induced electronic circular dichroism (ECD) spectra analyses. The integrated ¹H and ¹³C NMR data of three new natural products 5–7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5–9, and 18 displayed significant inhibitory activities against hCE 2 with IC₅₀ values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78, 29.78 ± 0.48, 18.86 ± 1.87, and 20.72 ± 1.51 µM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.     

Two new alkaloid metabolites produced by endophytic fungus Stagonosporopsis oculihominis isolated from Dendrobium huoshanense

Two new alkaloids (1–2), together with six known compounds (3–8), were isolated from cultures of the endophytic fungus Stagonosporopsis oculihominis. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRMS analyses. The absolute configurations of 1 was determined by the comparison of experimental and theoretical electronic circular dichroism spectra. The new compounds were investigated for their cytotoxicity against five human cancer cell lines.     

Bioactive metabolites produced by Chaetomium globosum,an endophytic fungus isolated from Ginkgo biloba

A novel cytotoxic chlorinated azaphilone derivative named chaetomugilin D (1), together with three known metabolites, chaetomugilin A (2), chaetoglobosins A (3) and C (4), has been isolated by a bioassay-guided fractionation from the EtOAc extract of the cultures of Chaetomium globosum, an endophytic fungus found in the leaves of Ginkgo biloba. Structure of 1 was established by analyses of spectroscopic methods, including 2D-NMR experiments (COSY, NOESY, HMQC, and HMBC). Compounds 1–4 displayed significant growth inhibitory activity against the brine shrimp (Artemia salina) and Mucor miehei.     

Toxic polyketides produced by Fusarium sp., an endophytic fungus isolated from Melia azedarach

A new isocoumarin derivative named fusariumin (1), together with two known related resorcylic acid lactones aigialomycin D (2) and pochonin N (3), has been isolated from the cultures of Fusarium sp. LN-10, an endophytic fungus originated from the leaves of Melia azedarach. Their structures were established on the basis of extensive spectroscopic analyzes including 1D- and 2D- NMR (¹H-¹H COSY, HSQC, HMBC, and NOESY) experiments. Compounds 1-3 displayed significant growth inhibitory activity against the brine shrimp (Artemia salina).     

光照和培养基对内生真菌棘豆链格孢Alternaria oxytropis苦马豆素含量的影响

以小花棘豆内生真菌棘豆链格孢Alternaria oxytropis野生株OW7.8及其酵母氨酸还原酶基因缺失突变株M1为材料,研究它们在不同培养基上和不同光照下菌落生长速率与苦马豆素含量。结果表明：OW7.8在胡萝卜葡萄糖琼脂培养基上暗培养时生长速度最快,为(2.57±0.17)mm/d,而M1则在马铃薯葡萄糖琼脂培养基上暗培养时生长速度最快,为(4.93±0.10mm)/d。不同培养基和光照条件下,相同菌株苦马豆素的含量差异不显著（P>0.05）;不同菌株在相同培养条件下其苦马豆素含量差异显著（P<0.05）。     

NF kappa B inhibitors and antitrypanosomal metabolites from endophytic fungus Penicillium sp. isolated from Limonium tubiflorum

Chemical investigation of the endophytic fungus Penicillium sp. isolated from Limonium tubiflorum growing in Egypt afforded four new compounds of polyketide origin, including two macrolides, penilactone (1) and 10,11-epoxycurvularin (2), a dianthrone, neobulgarone G (7), and a sulfinylcoumarin, sulfimarin (14), along with twelve known metabolites (3-6, 8-13, 15 and 16). The structures of all compounds were assigned by comprehensive spectral analysis (1D and 2D NMR) and mass spectrometry. Compounds 3, 4, 13 and 16 showed pronounced antitrypanosomal activity with mean MIC values ranging from 4.96 to 9.75 ??M. Moreover, when tested against a panel of three human tumor cell lines compounds 3, 4, 6 and 12 showed selective growth inhibition against Jurkat and U937 cell lines with IC₅₀ values ranging from 1.8 to 13.3 ??M. The latter compounds also inhibited TNF??-induced NF-??B activity in K562 cells with IC₅₀ values ranging from 1.6 to 10.1 ??M, respectively.     

First report of secondary metabolites,Violaceol I and Violaceol II produced by endophytic fungus,Trichoderma polyalthiae and their antimicrobial activity

Bioactive compounds of endophytic fungus Trichoderma polyalthiae were extracted from culture broth media. The crude extracts showed strong antimicrobial activity against human pathogens. Biologically active compounds were isolated and purified by chromatographic methods. The structures of the pure compounds were elucidated by spectroscopic methods. They were identified as Violaceol I and Violaceol II. These compounds were detected as secondary metabolites produced by this genus for the first time. Violaceol I and II had a broad spectrum of antimicrobial activity against human pathogens, including Gram-positive bacteria (Staphylococcus saprophyticus, Staphylococcus aureus, Methicillin-Resistant S. aureus, Bacillus subtilis, Bacillus cereus) and Gram-negative bacteria (Salmonella typhimurium, Shigella sonnei) and Candida albicans. Violaceol I exhibited Minimal Inhibitory Concentration (MIC) values (<9.765–156.25 μg/mL) that were higher than Violaceol II (<9.765–312.5 μg/mL). Additionally, the MIC value of the phenol violaceol from this taxon was lower than the previous reports.     

Synthesis and evaluation of d-gluco-pyranocyclopropyl amines as potential glucosidase inhibitors

In the recent past sugar-derived cyclopropylamines were proposed as structurally new glycosidase inhibitors. In this Letter we report our efforts in the synthesis of a set of α-glucose configured oxabicyclo[4.1.0] heptanes, based on this hypothesis, bearing an amine substituent on the propyl ring and reveal that their inhibitory potential towards a range of mammalian glucosidases is modest.     

Introducing Alternaria tenuissima SBUp1, as an endophytic fungus of Ferula assa-foetida from Iran,which is a rich source of rosmarinic acid

Endophytic fungi are the endogenous micro-organisms to interacting with the plant cells, which do not exhibit any symptoms on the host plant and may produce some of the main secondary metabolites of the host plant cells. Ferula assa-foetida is a perennial and endemic medicinal plant of Iran, which is a rich source of sesquiterpene, coumarins, polysulfides and phenolic acids. In this study, 28 endophytic fungi isolates including Fusarium (60·7%), Aspergillus (7·1%), Alternaria (17·9%) and Plectosphaerella (7·1%) were isolated from F. assa-foetida root (57·1%), stem (32·1%) and leaf (10·8%) collected from Parvand protected area. Subsequently, their ability to produce phenolic acids was evaluated. The high amounts of total phenol (326·09 mg g⁻¹ of dry weight, DW), total flavonoid (901·11 mg g⁻¹ DW) and antioxidant activity (247·96 mg l⁻¹) were found in the supernatant fluid of SBUp1 isolate. The high-performance liquid chromatography analysis of 14 phenolic acids showed that rosmarinic acid (RA) is the main phenolic acid in the supernatant fluid of SBUp1 by 64·11 mg g⁻¹ DW confirmed by the liquid chromatography coupled with mass spectrometric analysis. According to morphological identification followed by phylogenetic study based on internal transcribed spacer (ITS) sequencing (ITS1-5.8S-ITS2) analysis, the SBUp1 isolate was identified as Alternaria tenuissima. Eventually, to our knowledge, it is the first document confirming A. tenuissima as an endophytic fungus of F. assa-foetida, which is a rich source of RA.     

Secondary metabolites produced by an endophytic fungus Cordyceps ninchukispora from the seeds of Beilschmiedia erythrophloia Hayata

Four new amide derivatives, designated as cordycepiamides A–D (1–4), together with 14 known compounds (5–18), were isolated from the EtOAc-soluble fraction of the 95% EtOH extract of long-grain rice fermented with the endophytic fungus C. ninchukispora BCRC 31900, derived from the seeds of medicinal plant Beilschmiedia erythrophloia Hayata. Their structures were elucidated by means of spectroscopic and mass-spectrometric analyses, particularly 1D and 2D NMR spectroscopy as well as HRESIMS. All known isolates except 11, were isolated for the first time from this species. The antiinflammatory activities of selected isolated 10 compounds (1, 2, 4–6, 9–12, and 14) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compound 3→4 was shown to have modest anti-inflammatory effects through inhibition of NO production in LPS-stimulated RAW264.7 cells.