Two New Isocoumarins Isolated from the Marine-Sponge-Derived Fungus Setosphaeria sp. SCSIO41009.

Two new dihydroisocoumarins, exserolides L and M (1 and 2), along with six known compounds (3-8) were isolated from the extract of the marine-sponge-derived fungus Setosphaeria sp. SCSIO41009. Their structures were established by spectroscopic analyses. The absolute configurations of two new compounds were determined by modified Mosher's method and ECD data. Compounds 1 and 4 showed significant antiviral activities against A/Puerto Rico/8/34 H274Y (H1 N1) with IC50 values of 4.07±0.76 µM and 20.06±4.85 µM, respectively.

Structurally various p-terphenyls with neuraminidase inhibitory from a sponge derived fungus Aspergillus sp. SCSIO41315.

Guided by Global Natural Products Social molecular networking, 14 new p-terphenyl derivatives, asperterphenyls A-N (1-14), together with 20 known p-terphenyl derivatives (15-34), were obtained from a sponge derived fungus Aspergillus sp. SCSIO41315. Among them, new compounds 2-8 and 15-17 were ten pairs of enantiomers. Comprehensive methods such as chiral-phase HPLC analysis, ECD calculations and X-ray diffraction analysis were applied to determine the absolute configurations. Asperterphenyls B (2) and C (3) represented the first reported natural p-terphenyl derivatives possessing a dicarboxylic acid system. Asperterphenyl A (1) displayed neuraminidase inhibitory activity with an IC50 value of 1.77 ± 0.53 µM and could efficiently inhibit infection of multiple strains of H1N1 with IC50 values from 0.67 ± 0.28 to 1.48 ± 0.60 µM through decreasing viral plaque formation in a dose-dependent manner, which suggested that asperterphenyl A (1) might be exploited as a potential antiviral compound in the pharmaceutical fields.

Pestalotiopols E-J, Six New Polyketide Derivatives from a Marine Derived Fungus Pestalotiopsis sp. SWMU-WZ04-1.

Chemical epigenetic cultivation of the sponge-derived fungus Pestalotiopsis sp. SWMU-WZ04-1 contributed to the identification of twelve polyketide derivatives, including six new pestalotiopols E-J (1-6) and six known analogues (7-12). Their gross structures were deduced from 1D/2D NMR and HRESIMS spectroscopic data, and their absolute configurations were further established by circular dichroism (CD) Cotton effects and the modified Mosher's method. In the bioassay, the cytotoxic and antibacterial activities of all compounds were evaluated. Chlorinated benzophenone derivatives 7 and 8 exhibited inhibitory effects on Staphylococcus aureus and Bacillus subtilis, with MIC values varying from 3.0 to 50 µg/mL. In addition, these two compounds were cytotoxic to four types of human cancer cells, with IC50 values of 16.2~83.6 µM. The result showed that compound 7 had the probability of being developed into a lead drug with antibacterial ability.

New Carboxamides and a New Polyketide from the Sponge-Derived Fungus Arthrinium sp. SCSIO 41421.

New carboxamides, (±)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other fifteen known natural products (4-18). Their structures including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, calculated electronic circular dichroism (ECD), as well as quantum-chemical NMR calculations. Preliminary bioactivity screening and molecular docking analysis revealed that several natural products exhibited obvious enzyme inhibitory activities against acetylcholinesterase (AChE), such as 2,3,6,8-tetrahydroxy-1-methylxanthone (4) with an inhibitory rate 86% at 50 µg/mL.

Anti-Inflammatory Polyketide Derivatives from the Sponge-Derived Fungus Pestalotiopsis sp. SWMU-WZ04-2.

Five undescribed polyketide derivatives, pestaloketides A-E (1-5), along with eleven known analogues (6-16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 µM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 µM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads.

Two New Alkaloids and a New Butenolide Derivative from the Beibu Gulf Sponge-Derived Fungus Penicillium sp. SCSIO 41413.

Marine sponge-derived fungi have been proven to be a prolific source of bioactive natural products. Two new alkaloids, polonimides E (1) and D (2), and a new butenolide derivative, eutypoid F (11), were isolated from the Beibu Gulf sponge-derived fungus, Penicillium sp. SCSIO 41413, together with thirteen known compounds (3-10, 12-16). Their structures were determined by detailed NMR, MS spectroscopic analyses, and electronic circular dichroism (ECD) analyses. Butenolide derivatives 11 and 12 exhibited inhibitory effect against the enzyme PI3K with IC50 values of 1.7 µM and 9.8 µM, respectively. The molecular docking was also performed to understand the inhibitory activity, while 11 and 12 showed obvious protein/ligand-binding effects to the PI3K protein. Moreover, 4 and 15 displayed obvious inhibitory activity against LPS-induced NF-κB activation in RAW264.7 cells at 10 µM.

Inhibitory Effects of Epipolythiodioxopiperazine Fungal Metabolites on Isocitrate Lyase in the Glyoxylate Cycle of Candida albicans.

Four epipolythiodioxopiperazine fungal metabolites (1-4) isolated from the sponge-derived Aspergillus quadrilineatus FJJ093 were evaluated for their capacity to inhibit isocitrate lyase (ICL) in the glyoxylate cycle of Candida albicans. The structures of these compounds were elucidated using spectroscopic techniques and comparisons with previously reported data. We found secoemestrin C (1) (an epitetrathiodioxopiperazine derivative) to be a potent ICL inhibitor, with an inhibitory concentration of 4.77 ± 0.08 µM. Phenotypic analyses of ICL-deletion mutants via growth assays with acetate as the sole carbon source demonstrated that secoemestrin C (1) inhibited C. albicans ICL. Semi-quantitative reverse-transcription polymerase chain reaction analyses indicated that secoemestrin C (1) inhibits ICL mRNA expression in C. albicans under C2-assimilating conditions.

Heterocornols from the Sponge-Derived Fungus Pestalotiopsis heterocornis with Anti-Inflammatory Activity.

One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q-X (1-8), one new ceramide (9), and three known analogues (10-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 µg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity.

Cyclopeptide Derivatives from the Sponge-Derived Fungus Acremonium persicinum F10.

Cyclopeptides usually play a pivotal role, either in the viability or virulence of fungi. Two types of cyclopeptides, six new hydroxamate siderophore cyclohexapeptides (1-6), including acremonpeptides E and F, and their complexes with aluminum and ferric ions; one new cyclic pentapeptolide, aselacin D (9); together with a known compound, aselacin C (10), were isolated and characterized from the sponge-derived fungus Acremonium persicinum F10. In addition, two new siderophore analogues chelating gallium ions (Ga3+), Ga (III)-acremonpeptide E (7) and Ga (III)-acremonpeptide F (8), using isolated acremonpeptides E and F, were prepared. The planar structures of 1-10 were elucidated by HRESIMS and (1D and 2D) NMR. The absolute configurations of amino acids were determined by means of the advanced Marfey's method and X-ray single-crystal diffraction analysis. X-ray fluorescence (XRF) spectrometer was performed to disclose the elements of compound 1, indicating the existence of aluminum (Al). Al (III)-acremonpeptides E (1), Ga (III)-acremonpeptides E (5), Al (III)-acremonpeptide F (7), and Ga (III)-acremonpeptide F (8) displayed high in vitro anti-fungal activities, which are comparable to amphotericin B, against Aspergillus fumigatus and Aspergillus niger.

Apoptotic Activity of New Oxisterigmatocystin Derivatives from the Marine-Derived Fungus Aspergillus nomius NC06.

Sponge-derived fungi have recently attracted attention as an important source of interesting bioactive compounds. Aspergillus nomius NC06 was isolated from the marine sponge Neopetrosia chaliniformis. This fungus was cultured on rice medium and yielded four compounds including three new oxisterigmatocystins, namely, J, K, and L (1, 2, and 3), and one known compound, aspergillicin A (4). Structures of the compounds were elucidated by 1D and 2D NMR spectroscopy and by high-resolution mass spectrometry. The isolated compounds were tested for cytotoxic activity against HT 29 colon cancer cells, where compounds 1, 2, and 4 exhibited IC50 values of 6.28, 15.14, and 1.63 µM, respectively. Under the fluorescence microscope by using a double staining method, HT 29 cells were observed to be viable, apoptotic, and necrotic after treatment with the cytotoxic compounds 1, 2, and 4. The result shows that compounds 1 and 2 were able to induce apoptosis and cell death in HT 29 cells.

Antibacterial Cyclic Tripeptides from Antarctica-Sponge-Derived Fungus Aspergillus insulicola HDN151418.

Three new aspochracin-type cyclic tripeptides, sclerotiotides M-O (1-3), together with three known analogues, sclerotiotide L (4), sclerotiotide F (5), and sclerotiotide B (6), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus, Proteus species, Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Edwardsiella tarda, MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.

Antibacterial Polyketides from Antarctica Sponge-Derived Fungus Penicillium sp. HDN151272.

Three new polyketides, ketidocillinones A-C (1-3), were discovered from the extract of an Antarctica sponge-derived fungus Penicillium sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS. The absolute configuration of compound 3 was established by using ECD calculation. Compounds 1-3 can be slowly oxidized to quinone form when exposed to air. Ketidocillinones B and C (2 and 3) exhibited potent antibacterial activity against Pseudomonas aeurigenosa, Mycobacterium phlei, and MRCNS (methicillin-resistant coagulase-negative staphylococci) with MIC values ranging from 1.56 to 25.00 µg/mL.

A new lateral root growth inhibitor from the sponge-derived fungus Aspergillus sp. LS45.

Two new γ-lactones, aspergilactones A (1) and B (2), were discovered along with two known compounds, annularin A (3) and pericoterpenoid A (4), from a culture of the sponge-associated fungus Aspergillus sp. LS45. The planar structures of 1-4 were characterized using comprehensive spectroscopic methods and comparison with literature data. The absolute configurations of 1 and 2 were determined by comparison of electronic circular dichroism (ECD) spectroscopic and optical rotation data with those of known analogues as well as calculated ECD analysis. Compounds 1-4 were tested in a variety of bioassays, and both 1 and 4 exhibited significant inhibition against the lateral root growth of Arabidopsis thaliana Columbia-0 at a concentration of 100 µM. In addition, the in vitro cytotoxic activities of 1-4 against six human cancer cell lines CCRF-CEM, K562, BGC823, AGS, HCT-116 and MDA-MB-231 were evaluated. Compound 4 showed moderate inhibitory effects on CCRF-CEM and K562 cancer cell lines with IC50 values of 13.8 ±â€¯1.6 and 12.9 ±â€¯2.5 µM, respectively. However, compounds 1-4 did not show any notable AChE inhibitory activity in vitro.

New Alkaloids and Polyketides from the Marine Sponge-Derived Fungus Penicillium sp. SCSIO41015.

The sponge-derived fungus Penicillium sp. SCSIO41015 cultured on solid rice medium yielded twenty-one compounds (1-21), including two new alkaloids (1 and 2) and one new pyrone derivative (3). Their structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. Their absolute configurations were established by single-crystal X-ray diffraction analysis and comparison of the experimental with reported specific rotation values. Compound 16 exhibited selective cytotoxic activity against the human gastric cancer cells MGC803, with IC50 value of 5.19 µM. Compounds 9 and 18 showed weak antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, respectively, both with MIC values of 57 µg/mL. Furthermore, compound 16 displayed potent antibacterial activity against S. aureus with an MIC value of 3.75 µg/mL.

Perylenequione Derivatives with Anticancer Activities Isolated from the Marine Sponge-Derived Fungus, Alternaria sp. SCSIO41014.

Seven new secondary metabolites classified as two perylenequinone derivatives (1 and 2), an altenusin derivative (3), two phthalide racemates (4 and 5), and two phenol derivatives (6 and 7), along with twenty-one known compounds (8⁻28) were isolated from cultures of the sponge-derived fungus, Alternaria sp. SCSIO41014. The structures and absolute configurations of these new compounds (1⁻7) were determined by spectroscopic analysis, X-ray single crystal diffraction, chiral-phase HPLC separation, and comparison of ECD spectra to calculations. Altertoxin VII (1) is the first example possessing a novel 4,8-dihydroxy-substituted perylenequinone derivative, while the phenolic hydroxy groups have commonly always substituted at C-4 and C-9. Compound 1 exhibited cytotoxic activities against human erythroleukemia (K562), human gastric carcinoma cells (SGC-7901), and hepatocellular carcinoma cells (BEL-7402) with IC50 values of 26.58 ± 0.80, 8.75 ± 0.13, and 13.11 ± 0.95 µg/mL, respectively. Compound 11 showed selectively cytotoxic activity against K562, with an IC50 value of 19.67 ± 0.19 µg/mL. Compound 25 displayed moderate inhibitory activity against Staphylococcus aureus with an MIC value of 31.25 µg/mL.

Two New Altenusin/Thiazole Hybrids and a New Benzothiazole Derivative from the Marine Sponge-Derived Fungus Alternaria sp. SCSIOS02F49.

Two novel altenusin-thiazole hybrids named altenusinoides A and B (1 and 2), a new benzothiazole derivative (3), and three known altenusin derivatives (4⁻6) have been obtained from the solid culture of the marine sponge-derived fungal strain, Alternaria sp. SCSIOS02F49. The structures of these new compounds were characterized by NMR, HRESIMS, and X-ray single crystal analysis. Compounds 1 and 2 possess an unusual altenusin-thiazole-fused skeleton core (6/6/5), and compound 3 represents the first benzothiazole derivative from fungi. Compounds 4 and 5 showed significant DPPH free-radical-scavenging activities with the prominent IC50 values of 10.7 ± 0.09 µM and 100.6 ± 0.025 µM, respectively. Additionally, compound 5 exhibited COX-2 inhibitory activity with an IC50 value of 9.5 ± 0.08 µM.

5-Hydroxycyclopenicillone, a New ß-Amyloid Fibrillization Inhibitor from a Sponge-Derived Fungus Trichoderma sp. HPQJ-34.

Abstract: A new cyclopentenone, 5-hydroxycyclopeni cillone (1), was isolated together with three known compounds, ar-turmerone (2), citreoisocoumarin (3), and 6-O-methyl-citreoisocoumarin (4), from a culture of the sponge-derived fungus Trichoderma sp. HPQJ-34. The structures of 1-4 were characterized using comprehensive spectroscopic analyses. The absolute configuration of 1 was determined by comparison of electronic circular dichroism (ECD) spectra with literature values used for the reported analogue, cyclopenicillone (5), which was not isolated in this research. Compound 1 was shown to scavenge 2,2-diphenyl-1-picrylhydrazyl free radicals, and decrease ß-amyloid (Aß) fibrillization in vitro. Moreover, 1 significantly reduced H2O2-induced neurotoxicity in SH-SY5Y cells. These findings suggested that compound 1, a newly discovered cyclopentenone, has moderate anti-oxidative, anti-Aß fibrillization properties and neuroprotective effects, and might be a good free radical scavenger.

[Study on metabolites from a sponge-derived fungus].

We have carried out the investigation on a sponge-derived fungus,which was identified as Emericella variecolor from the south sea of China. Two new chemical constituents,(+)-2-acetyl-dihydroterrein (1) and (+)-3-acetyl-dihydroterrein (2),with four known compounds,anditomin (3),andilesin A (4),andilesin C (5) and andilesin B (6),were isolated from this fungus by column chromatography over silica gel, Sephadex LH-20, and ODS. The structures of 1 and 2 were elucidated by spectroscopic methods including NMR,HR-ESI-MS,and CD.

Naphthalenones and Depsidones from a Sponge-Derived Strain of the Fungus Corynespora cassiicola.

Two new naphthalenones, corynenones A and B (1 and 2), and one new depsidone, corynesidone E (3), together with one known depsidone, corynesidone A (4) and two known diphenyl ethers, corynethers A (5) and B (6), were isolated from the sponge-derived fungus Corynespora cassiicola XS-20090I7. Their structures including absolute configurations were determined by spectroscopic data and electronic circular dichroism (ECD) spectra. Compounds 4 and 5 showed cytotoxicity against human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cell lines.

Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40.

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge-derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1-7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC50 values of 6.2 ± 0.08 and 8.9 ± 0.3 µM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC50 value of 3.5 ± 1.3 µM.