Gorgonian-derived Fungus Aspergillus Research Articles

Prenylated notoamide-type alkaloids isolated from the fungus Aspergillus sclerotiorum and their inhibition of NLRP3 inflammasome activation and antibacterial activities

Notoamides are a family of prenylated indole alkaloids with unusual ring systems and possessing a range of significant pharmaceutical activities. Based on LC-MS/MS and genome orientations, ten undescribed notoamide-type alkaloids namely sclerotiamides I-R were isolated from a marine gorgonian-derived fungus Aspergillus sclerotiorum LZDX-33-4. Their structures were determined by extensive spectroscopic data, in association with ECD data and single-crystal X-ray diffraction for configurational assignments. Bioassays resulted in sclerotiamide J along with five analogs possessing inhibitory effects against LDH and IL-1β expression in BV-2 cells. Further investigation revealed that sclerotiamide J significantly inhibited NLRP3 inflammasome activation and blocked NLRP3 inflammasome-induced pyroptosis via amelioration of mitochondria damage. In addition, sclerotiamide L exhibited potent inhibition against pathogenic Staphylococcus aureus ATCC 29213 with MIC value of 4.0 μM and the growth of MRSA T144 and Enterococcus faecalis ATCC 29212. This study extends the chemical diversity of notoamide-type alkaloids, and provides potential anti-inflammasome and antibacterial lead compounds for further structure optimization.

Sclerotiamides C-H, Notoamides from a Marine Gorgonian-Derived Fungus with Cytotoxic Activities.

Bioassay-guided fractionation in association with LC-MS and NMR detection led to the isolation of six new alkaloids, sclerotiamides C-H (1-6), from the marine gorgonian-derived fungus Aspergillus sclerotiorum LZDX-33-4. Their structures were determined from extensive spectroscopic data, including ECD data and single-crystal X-ray diffraction analysis for configurational assignments. Sclerotiamides C (1) and D (2) are notoamide-type alkaloids with the incorporation of a unique 2,2-diaminopropane unit, and sclerotiamides E (3) and F (4) are unprecedented notoamide hybrids with a new coumarin unit. Sclerotiamide H (6) represents a new highly oxidized notoamide scaffold. Sclerotiamides C and F showed significant inhibition against a panel of tumor cell lines with IC50 values ranging from 1.6 to 7.9 μM. Sclerotiamide C induces apoptosis in HeLa cells by arresting the cell cycle, activating ROS production, and regulating apoptosis-related proteins in the MAPK signaling pathway. The present study extends the scaffold diversity of the notoamides and provides a potential lead for the development of a cytotoxic agent.

Anti-HSV-1 activity of Aspergillipeptide D, a cyclic pentapeptide isolated from fungus Aspergillus sp. SCSIO 41501

BackgroundHerpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D.MethodsThe anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins.ResultsPlaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread.ConclusionsOur results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains.

A new epimer of azaphilone derivative pinophilin B from the gorgonian-derived fungus Aspergillus fumigatus 14–27

A new epimer of azaphilone derivative pinophilin B, epi-pinophilin B (1), and three known analogues (2–4) were obtained from the culture of the gorgonian-derived fungus Aspergillus fumigatus 14–27. The structures of 1–4, including their relative configurations were determined by extensive spectroscopic analysis and comparing with literature data. The absolute configuration of 1 was determined by electronic circular dichroism (ECD) and optical rotatory (OR) calculations methods. Compounds 1–4 were isolated from A. fumigatus for the first time. Their antibacterial and cytotoxic activities were also evaluated.

Secondary Metabolites and their Bioactivities from the Gorgonian-Derived Fungus Aspergillus versicolor

Secondary Metabolites and their Bioactivities from the Gorgonian-Derived Fungus Aspergillus versicolor

New alkaloids and isocoumarins from the marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501

Two new β-carboline alkaloids, aspergillspins A-B (1–2), three new quinolone alkaloids, aspergillspins C-E (3–5), and two new isocoumarins, aspergillspins F-G (6–7), together with four known alkaloids were isolated from the marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501. Their structures were identified by spectroscopic analysis, and the absolute configurations of several chiral carbons in 2 and 3 were further established by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Their cytotoxic and antibacterial activities were also evaluated.

Secondary Metabolites Isolated from the Gorgonian-Derived Fungus Aspergillus ruber and Their Antiviral Activity

Secondary Metabolites Isolated from the Gorgonian-Derived Fungus Aspergillus ruber and Their Antiviral Activity

Cytochalasins from the Gorgonian-Derived Fungus Aspergillus sp. XS-2009-0B15

Cytochalasins from the Gorgonian-Derived Fungus Aspergillus sp. XS-2009-0B15

Antiviral peptides from marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501

A new cyclic pentapeptide and three new linear peptides, namely, aspergillipeptides D–G (1–4), were isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501. Their structures were elucidated by spectroscopic analysis, and their absolute configurations were confirmed by Marfey’s method. Compounds 1 and 2 showed evident antiviral activity against herpes simplex virus type 1 (HSV-1) with IC50 values of 9.5 and 19.8µM under their non-cytotoxic concentrations against a Vero cell line, respectively, and 1 also had antiviral activity against acyclovir-resistant clinical isolates of HSV-1.

Versicotides D–F, new cyclopeptides with lipid-lowering activities

Versicotides D–F, new cyclopeptides were isolated from a gorgonian-derived fungusAspergillus versicolorLZD-14-1 and showed lipid-lowering effects.

Versiquinazolines A-K, Fumiquinazoline-Type Alkaloids from the Gorgonian-Derived Fungus Aspergillus versicolor LZD-14-1.

Eleven fumiquinazoline-type alkaloids, namely, versiquinazolines A-K (1-11), along with cottoquinazolines B-D, were isolated from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1. Their structures were determined by extensive analyses of the spectroscopic data (1D and 2D NMR, HRESIMS), in addition to the experimental and calculated ECD data and X-ray single-crystal diffraction analysis for the assignments of the absolute configurations. Versiquinazolines A, B, and F (1, 2, and 6), bearing a methanediamine or an aminomethanol unit and representing a unique subtype of fumiquinazolines, were found from nature for the first time. Possible biogenetic relationships of the versiquinazolines are postulated. In addition, the structures of cottoquinazolines B (12), D (13), and C (14) should be revised to the enantiomers. Compounds 1, 2, 7, and 11 exhibited inhibitory activities against thioredoxin reductase (IC50 values ranging from 12 to 20 μM).

Anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the gorgonian-derived fungus Aspergillus sp. XS-20090B15.

Two new prenylated dihydroquinolone derivatives, 22-O-(N-Me-l-valyl)aflaquinolone B (1) and 22-O-(N-Me-l-valyl)-21-epi-aflaquinolone B (2), and two known analogues, aflaquinolones A (3) and D (or a diastereomer of D, 4), were isolated from the mycelia of a gorgonian-derived Aspergillus sp. fungus. The structures of the new compounds were elucidated by spectroscopic methods, ECD spectra, Marfey's method, and chemical conversion. Compounds 1 and 2 display an unusual esterification of N-Me-l-Val to the side-chain prenyl group. Compound 2 exhibited outstanding anti-RSV activity with an IC50 value of 42 nM, approximately 500-fold stronger than that of the positive control ribavirin (IC50 = 20 μM), and showed a comparatively higher therapeutic ratio (TC50/IC50 = 520).

A New Anthraquinone Derivative from a Gorgonian-Derived Fungus Aspergillus sp.

One new anthraquinone derivative, named 8-O-methylnidurufin (1), together with five known analogues (2–6), have been isolated from a gorgonian-derived fungus, Aspergillus sp. The structures were elucidated by combined spectroscopic methods including 1D and 2D NMR spectral data. All isolated metabolites were evaluated for their cytotoxic and antibacterial activities in vitro. Compound 2 showed significant cytotoxic activity against K562 and HL-60 cell lines with IC50 values of 0.87 and 1.46 μM, respectively.

Lumazine peptides penilumamides B-D and the cyclic pentapeptide asperpeptide A from a gorgonian-derived Aspergillus sp. fungus.

Three new lumazine peptides, penilumamides B-D (2-4), and one known analogue, penilumamide (1), together with a new cyclic pentapeptide, asperpeptide A (5), were isolated from the gorgonian-derived fungus Aspergillus sp. XS-20090B15. Among them, 2 was obtained from the feeding culture with l-methionine of this strain. All structures were elucidated by spectroscopic methods and chemical derivatization. Compounds 1-4 are rare lumazine peptides, of which 1 and 3 are formed from 2 by oxidation of the l-methionine residue.

New cyclic tetrapeptides and asteltoxins from gorgonian-derived fungus Aspergillus sp. SCSGAF 0076

Three new cyclic tetrapeptides, aspergillipeptides A–C (1–3), and one new asteltoxin B (4) were isolated from a culture broth of gorgonian-derived fungal strain Aspergillus sp. SCSGAF 0076. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of aspergillipeptides A–C were determined by Marfey's method. Aspergillide C (3) showed strong antifouling activity against Bugula neritina larvae settlement with LC50/EC50>25.

New mycotoxins from marine-derived fungus Aspergillus sp. SCSGAF0093

Nine mycotoxins including six aspergillic acid group toxins, aluminiumneoaspergillin (1), zirconiumneoaspergillin (2), aspergilliamide (3), ferrineoaspergillin (5), flavacol (6), neoaspergillic acid (7), and three ochratoxins, ochratoxin A n-butyl ester (4), ochratoxin A (8), ochratoxin A methyl ester (9), were isolated from the fermentation broth of marine gorgonian derived fungus Aspergillus sp. SCSGAF0093. Four of them (1–4) were new mycotoxins, and their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. The bio-toxicity of compounds 1–9 were determined by brine shrimp lethality bioassay with median lethal concentration (LC50) values of 2.59–205.67μM. This was the first report about zirconium complex obtained from nature and ochratoxins isolated from marine environment.

Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton from the gorgonian-derived fungus Aspergillus sp.

Two novel benzylazaphilone derivatives with an unprecedented carbon skeleton, aspergilone A (1), and its symmetrical dimer with a unique methylene bridge, aspergilone B (2), have been isolated from the culture broth of a marine-derived fungus Aspergillus sp. from a gorgonian Dichotella gemmacea. Their structures and relative stereochemistries of 1 and 2 were elucidated using a combination of NMR spectroscopy and X-ray crystallography. Compound 1 not only exhibited in vitro selective cytotoxicity but also showed potent antifouling activity.