Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC being 5.11 ± 0.53 μmol·L, and acted as a noncompetitive inhibitor based on kinetic analysis.
4-Butyrolactone ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology ; Animals ; Aspergillus ; chemistry ; Chemistry Techniques, Analytical ; Dipeptides ; chemistry ; isolation & purification ; pharmacology ; Enzyme Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Indoles ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Mycobacterium tuberculosis ; drug effects ; Peptides ; chemistry ; isolation & purification ; pharmacology ; Polyketides ; chemistry ; isolation & purification ; pharmacology ; Porifera ; microbiology ; Protein Tyrosine Phosphatases ; chemistry

OBJECTIVE: A strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. METHODS: Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. RESULTS: The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-a, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). CONCLUSION Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.
Animals ; Anti-Inflammatory Agents ; metabolism ; pharmacology ; Antioxidants ; metabolism ; pharmacology ; Aspergillus niger ; genetics ; isolation & purification ; metabolism ; Coumaric Acids ; metabolism ; pharmacology ; DNA, Fungal ; analysis ; Dietary Fiber ; microbiology ; Erythrocytes ; drug effects ; metabolism ; Fermentation ; Hep G2 Cells ; Humans ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; pharmacology ; Mice ; RAW 264.7 Cells ; Sheep ; Tumor Necrosis Factor-alpha ; metabolism

Chemical examination of an EtOAc extract of cultured Aspergillus versicolor fungus from deep-sea sediments resulted in the isolation of four xanthones, eight anthraquinones and five alkaloids, including a new xanthone, oxisterigmatocystin D (1) and a new alkaloid, aspergillusine A (13). High resolution electron impact mass spectrometry (HR-EI-MS), FT-IR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds, and the absolute configuration of compound 1 was established by its NMR features and coupling constant. Furthermore, the biosynthesis pathway of these xanthones and anthraquinones were deduced, and their antioxidant activity and cytotoxicity in human cancer cell lines (HTC-8, Bel-7420, BGC-823, A549, and A2780) were evaluated. The trolox equivalent antioxidant capacity (TEAC) assay indicated most of the xanthones and anthraquinones possessing moderate antioxidant activities. The Nrf2-dependent luciferase reporter gene assay revealed that compounds 6, 7, 9, and 12 potentially activated the expression of Nrf2-regulated gene. In addition, compounds 5 and 11 showed weak cytotoxicity on A with the IC values of 25.97 and 25.60 μmol·L, respectively.
Anthraquinones ; Antioxidants ; chemistry ; isolation & purification ; metabolism ; pharmacology ; Aspergillus ; chemistry ; genetics ; isolation & purification ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Gene Expression ; drug effects ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Seawater ; microbiology ; Spectroscopy, Fourier Transform Infrared ; Xanthones ; chemistry ; isolation & purification ; metabolism ; pharmacology

BACKGROUND: We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. METHODS: A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and beta-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. RESULTS: ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by beta-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of > or =2 microg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was < or =75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). CONCLUSIONS: Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.
Amphotericin B/*pharmacology ; Antifungal Agents/*pharmacology ; Aspergillus/*drug effects/isolation & purification ; DNA, Fungal/chemistry/genetics/metabolism ; Hospitals ; Humans ; Microbial Sensitivity Tests ; Mycoses/diagnosis/microbiology ; Republic of Korea ; Sequence Analysis, DNA ; Tubulin/genetics

The present study was designed to isolate and purify chemical constituents from solid culture of endophyte Aspergillus terreus LQ, using silica gel column chromatography, gel filtration with Sephadex LH-20, and HPLC. Fumigaclavine I (1), a new alkaloid, was obtained, along with seven known compounds, including fumigaclavine C (2), rhizoctonic acid (3), monomethylsulochrin (4), chaetominine (5), spirotryprostatin A (6), asperfumoid (7), and lumichrome (8). The structure of compound 1 was elucidated by various spectroscopic analyses (UV, MS, 1D and 2D NMR). The in vitro cytotoxicity of compound 1 was determined by MTT assay in human hepatocarcinoma cell line SMMC-7721, showing weaker cytotoxicity, compared with cisplatin, a clinically used cancer chemotherapeutic agent.
Antineoplastic Agents ; chemistry ; isolation & purification ; Aspergillus ; chemistry ; isolation & purification ; Cell Line, Tumor ; Cell Survival ; drug effects ; Endophytes ; chemistry ; isolation & purification ; Ergot Alkaloids ; chemistry ; isolation & purification ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Oryza ; microbiology

A new steroid with a long cross-conjugation structure, 15a-hydroxy-(22E, 24R)-ergosta-3, 5, 8 (14), 22-tetraen-7-one (1), was isolated from the marine-derived fungus Aspergillus aculeatus. Its structure was established by the extensive spectroscopic analyses, and its cytotoxicities against P388, HL-60, and PC-3 cell lines were measured in vitro.
Animals ; Aspergillus ; chemistry ; Cell Line, Tumor ; drug effects ; Cholestenones ; chemistry ; isolation & purification ; pharmacology ; HL-60 Cells ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Seawater ; microbiology

AIM: To investigate the chemical constituents of the endophytic fungus Verticillium sp. isolated from Rehmannia glutinosa. METHODS: The compounds were isolated and purified by repeated column chromatography, and their structures were determined on the basis of physicochemical properties and spectral analysis. Their cytotoxic and antifungal activities were evaluated. RESULTS: Ten compounds were obtained and their structures were identified as 2, 4-dihydroxy-2', 6-diacetoxy-3'-methoxy-5'-methyl-diphenyl ether (1), paecilospirone (2), α-acetylorcinol (3), 2-methoxy-1,8-dimethyl-xanthen-9-one (4), 4-hydroxy-α-lapachone (5), enalin A (6), 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (7), 4-hydroxyethyl-phenol (8), 2,4-dihydroxy-3,5,6-trimethyl- methylbenzoate (9), and 3-isopropenyl-(Z)-monomethyl maleate (10). CONCLUSIONS Compound 1 is a new diphenyl ether, and showed cytotoxic activity against HL-60 cells (IC50 2.24 μg · mL(-1)), and antifungal activities against Candida albicans (MIC 8 μg · mL(-1)) and Aspergillus fumigatus (MIC 16 μg · mL(-1)).
Antifungal Agents ; chemistry ; isolation & purification ; metabolism ; pharmacokinetics ; Antineoplastic Agents ; chemistry ; isolation & purification ; metabolism ; pharmacokinetics ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cell Line, Tumor ; Endophytes ; chemistry ; metabolism ; Humans ; Phenyl Ethers ; chemistry ; isolation & purification ; metabolism ; pharmacokinetics ; Rehmannia ; microbiology ; Verticillium ; chemistry ; metabolism

OBJECTIVETo isolate and characterize endophytic fungi from seven Dendrobium species, and detect their antimicrobial activities.

METHODFungal endophytes were isolated by strictly sterile sample preparation and fungal identification methods were based on their ITS ribosomal DNA (ITS rDNA gene) sequences. The agar well diffusion method was then employed to evaluate the antimicrobial activity against six pathogenic organisms and the phylogenetic tree of active isolates was constructed by the MEGA.

RESULTNinety-eight endophytic fungi obtained from seven Dendrobium spp., and among them twenty-four isolates, representing 11 genera and 14 species, displayed anti-microbial activities. The phylogenetic assay based on ITS-rDNA showed that 24 active isolates were sorted to 7 taxonomic orders: Hypocreales, Sordariales, Capnodiales, Eurotiales, Botryosphaeriales, Xylariales and Mucorales. The results of antimicrobial activity assay revealed that 1.02%, 10.2%, 18.4%, 1.02%, 1.02% and 10.2% of fermentation broths of 98 isolates displayed significant antimicrobial activities against E. coli, B. subtilis, S. aureus, C. albicans, C. neoformans and A. fumigatus, respectively. Four strains DL-R-3, DL-S-6, DG-R-10 and DN-S-1 displayed strong and broad antimicrobial spectrum.

CONCLUSIONEndophytic fungi associated with Dendrobium species have fungal diversity, and possess diverse antimicrobial activity.

Anti-Infective Agents ; metabolism ; pharmacology ; Aspergillus fumigatus ; drug effects ; Bacillus subtilis ; drug effects ; Base Sequence ; Biodiversity ; Candida albicans ; drug effects ; China ; Cryptococcus neoformans ; drug effects ; DNA, Fungal ; chemistry ; isolation & purification ; DNA, Ribosomal Spacer ; chemistry ; genetics ; Dendrobium ; microbiology ; physiology ; Endophytes ; classification ; genetics ; isolation & purification ; physiology ; Escherichia coli ; drug effects ; Fungi ; classification ; genetics ; isolation & purification ; physiology ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Phylogeny ; Plant Roots ; microbiology ; physiology ; Plant Stems ; microbiology ; physiology ; Sequence Alignment ; Sequence Analysis, DNA ; Staphylococcus aureus ; drug effects

Streptomyces S24 has broad spectrum against Aspergillus spp. in food and feed, such as Aspergillus flavus, Aspergillus niger and Asperegillus alutacells. The objective of this study was to improve the production of antifungal substances produced by S24 and to test their inhibitory effects on Aspergillus flavus. By using one-factor-at-a-time experiment and orthogonal design method, we optimized the fermentation medium. The composition of an optimized medium for the production of antifungal substances contained (g/L): starch soluble, 10; Glucose, 40; yeast extract, 8; soybean powder, 24; KH2PO4 4; and CaCO3 0.8. As a result, the productivity of antifungal substances could reach to 10 235.45 microg/mL, and this value was 2.81 times higher than that of initial medium before optimization. Additionally, inhibitory effects of the products on Aspergillus flavus were analyzed. Antagonistic tests indicated that the antifungal substances greatly inhibited mycelium growth and spores germination of Aspergillus flavus. We observed through microscope that the mycelia grew abnormally, such as contorting, bulging, vacuole increasing and the cytoplasmic contents inside effusing and the spores appeared unusual, such as gathering, deforming, cytoplasmic contents inside effusing and fracturing.
Adsorption ; Antifungal Agents ; chemistry ; isolation & purification ; pharmacology ; Aspergillus flavus ; drug effects ; growth & development ; Aspergillus niger ; drug effects ; growth & development ; Culture Media ; chemistry ; Food Contamination ; prevention & control ; Streptomyces ; chemistry ; growth & development ; metabolism

OBJECTIVETo research the isolation method, identification and screen for bioactivities endophytic fungi from ginkgo.

METHODEndophytic fungi from ginkgo were separated. By means of microdilution method, activities of endophytes against pathogenic fungi were tested. Then, using DPPH, the antioxidant activities were measured.

RESULTNine strains (16.1%) showed antifungal activities against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum and Aspergillus fumigatus. Among these bioactive strains, the growth of T. rubrum was strongly inhibited by T-1-2-1, as the MIC80 was equal to fluconazole, the positive control. Five strains (8.9%) showed antioxidant activities. Among them sample T-3-2-2 and T-6-5-7 showed the strongest antioxidant activities.

CONCLUSIONEndophytic fungi of ginkgo would be potential and rich resources for drug development.

Antifungal Agents ; pharmacology ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cryptococcus neoformans ; drug effects ; Fluconazole ; pharmacology ; Fungi ; chemistry ; drug effects ; isolation & purification ; Ginkgo biloba ; microbiology ; Microbial Sensitivity Tests ; Trichophyton ; drug effects