A New Fungal Metabolite, Sch 202596, with Inhibitory Activity in the Galanin Receptor GALR1 Assay (original) (raw)
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2013
During the research for bioactive secondary metabolites from microorganisms, the endophytic fungi Aspergillus fumigatus sp. isolate R7 was found to produce a set of promising bioactive compounds (1-10) after its large scale fermentation, working up and purification using a series of chromatographic techniques. Structural elucidation of the yielded compounds using intensive studies of their NMR ( 1 H, 13 C& 2D NMR) and mass (EI MS, ESI MS) spectrometry confirmed them as linoleic acid (1), R(-)-glycerol monolinoleate (2), bis-dethio-(bis-methyl-thio)-gliotoxin (3), fumiquinazoline-F (4), fumiquinazoline-D (5), (Z,Z)-N,N’-[1-[(4-Hydroxy-phenyl)methylene]-2-[(4-methoxy-phenyl)-methylene]-1,2-ethanediyl]-bis-formamide (6), pyrazoline-3-one trimer (7), Tricho-9-ene-2a,3a,11a,16-tetraol (8), 2’-deoxy-thymidine (9), and cerebroside A (10). In this article, taxonomical characterization, fermentation, structural characterization of the obtained metabolites were reported together with their an...
MAKARA of Science Series, 2012
The endophytic fungi Aspergillus fumigatus was isolated from the tissues of the fruits of Garcinia griffithii. The fungal strain was identified from the colony, and it was characteristic of cell morphology. The ethyl acetate extracts derived from fungus cultures showed major spots on TLC under UV light, which was continued to the isolation of the secondary metabolites. The structure of the isolated compound was elucidated on the basis of NMR analyses (1 H-NMR,
The Journal of Antibiotics, 1994
WIN64821, a nonpeptide neurokinin antagonist, was isolated from a strain of Aspergillus sp., SC319. The compound was produced in different fermentation media with greatest yields observed when the culture was grown in a synthetic medium supplemented with L-tryptophan and L-phenylalanine. After 6 days fermentation, yields greater than 600mg/liter were obtained. Two analogs of WIN64821 were also identified in the culture extracts and subsequently tested for biological activity. WIN64821 was the most potent compound isolated from this culture and exhibited activity as a substance P-binding inhibitor with submicromolar potency against the human neurokinin 1 receptor. 391
The Journal of Antibiotics, 2001
Four tachykinin (NK2) receptor inhibitors, SCH 378161 (1), SCH 217048 (2), SCH 378199 (3), and SCH 378167 (4) were isolated from the fermentation broth of a taxonomically unidentified fungus. These compounds were separated from the fermentation broth by ethyl acetate extraction. Purification and separation of the individual compoundswere achieved by NK2assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC. They were identified to be a family of depsipeptides by spectroscopic and degradation studies. Compounds1 and 3 contain proline and differ as an amide and acid whereas 2 and 4 contain pipecolic acid and differ in being an amide and acid. All of these compoundscontain an identical hydroxy acid. They are selective NK2 inhibitors with Ki values ranging from 27-982nM and demonstrate no activity at IO^m in the NKj and NK3assays. In addition, compounds 1 and 2 inhibited NKA-induced increases in the concentration of intracellular Ca2+, [Ca2+]j, in a CHOcell expressing the human NK2 receptor; this inhibition was competitive in nature with pA2 values of 7.2 and 7.5, respectively. These data demonstrate that these natural products are selective and competitive receptor antagonists of the humanNK2receptor.
Natural Product Research, 2016
Chemical investigation of Aspergillus japonicus CAM231, isolated from the leaf of Garcina preussii collected in Cameroon, yielded two new compounds; one pyrone derivative, hydroxy neovasinin (1) and one phenol derivative, asperolan (2), together with two known compounds neovasifurarone B (3) and variecolin (4). The structures of the two new compounds were established using intensive NMR spectroscopy and HRMS spectra in comparison with data found in literature. The structure of compound 1 was confirmed by singlecrystal X-ray crystallographic analysis in combination with NOESY experiment. The new compounds were screened for their cytotoxic and antibacterial properties; however, the tested compounds displayed no significant activities.
Galactomannoproteins of Aspergillus fumigatus
Eukaryotic Cell, 2005
Galactofuranose-containing molecules have been repeatedly shown to be important antigens among human fungal pathogens, including Aspergillus fumigatus. Immunogenic galactofuran determinants have been poorly characterized chemically, however. We reported here the characterization of two glycoproteins of A. fumigatus with an N-glycan containing galactofuranose. These proteins are a phospholipase C and a phytase. Chemical characterization of the N-glycan indicates that it is a mixture of Hex 5-13 HexNAc 2 oligosaccharides, the major molecular species corresponding to Hex 6-8 HexNAc 2. The N-glycan contained one galactofuranose unit that was in a terminal nonreducing position attached to the 2 position of Man. This single terminal nonreducing galactofuranose is essential for the immunoreactivity of the N-glycans assessed either with a monoclonal antibody that recognizes a tetra--1,5-galactofuran chain of galactomannan or with Aspergillus-infected patient sera.
Induction of new metabolites from sponge-associated fungus Aspergillus carneus by OSMAC approach
Fitoterapia, 2018
A comparative study on the metabolic profile of the sponge-associated fungus Aspergillus carneus using the OSMAC approach was conducted. The fungal strain was fermented on three different media including solid rice medium with or without sea salt and modified Czapek medium. Three new natural products, isopropylchaetominine (1), isoterrelumamide A (2) and 5′-epi-averufanin (3), together with fourteen known compounds (4-17) were isolated. The structures of the new compounds were established by 1D and 2D NMR spectroscopic analysis as well as by HRESIMS. Compound 2 was only found when the fungus was cultivated on modified Czapek medium, whereas compounds 4, 7, 11, 12, and 14 were only detected in fungal extracts from solid rice media lacking sea salt. Compounds 8 and 13 on the other hand were only found when A. carneus was cultured on solid rice with sea salt. The cytotoxic and antimicrobial activities of all isolated compounds were evaluated. Compounds 1, 9 and 17 showed strong cytotoxicity against the mouse lymphoma cell line L5178Y with IC 50 values of 0.4, 0.3 and 0.2 μM, respectively. In addition, compounds 3, 5 and 6 showed inhibitory activity against different Gram-positive bacterial strains with MIC values ranging from 2.3 to 18.4 μg/mL.
Fifty years of drug discovery from fungi
For the past 50 years, fungal secondary metabolites have revolutionized medicine yielding blockbuster drugs and drug leads of enormous therapeutic and agricultural potential. Since the discovery of penicillin, the first β-lactam antibiotic, fungi provided modern medicine with important antibiotics for curing life threatening infectious diseases. A new era in immunopharmacology and organ transplantation began with the discovery of cyclosporine. Other important drugs or products for agriculture derived from or inspired by natural products from fungi include statins, echinocandins and strobilurins. Moreover, fungal biotransformation of steroids for the industrial production of steroidal hormones represents one of the key successes in biotechnology. Given that estimations of fungal biodiversity exceed by far the number of already identified species, chances to find hitherto unidentified fungal species and novel bioactive fungal products are still high. Thus, further compounds with medicinal or agricultural potential from less investigated fungal taxa can be expected in the years to come.