2,3-Dimethoxycinnamic Acid from a Marine Actinomycete, a Promising Quorum Sensing Inhibitor in Chromobacterium violaceum.

An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated and purified from the extract and was identified as 2,3-dimethoxycinnamic acid (2,3-DCA) through spectral data analysis. At a concentration of 150 µg/mL, 2,3-DCA exhibited robust inhibitory effects on three QS-regulated traits of C. violaceum CV026: violacein production, swarming motility, and biofilm formation, with inhibition rates of 73.9%, 65.9%, and 37.8%, respectively. The quantitative reverse transcription polymerase chain reaction results indicated that 2,3-DCA can disrupt the QS system in C. violaceum CV026 by effectively suppressing the expression of QS-related genes, including cviR, vioA, vioB, and vioE. Molecular docking analysis revealed that 2,3-DCA hinders the QS system by competitively binding to the same binding pocket on the CviR receptor as the natural signal molecule N-hexanoyl-L-homoserine lactone. Collectively, these findings suggest that 2,3-DCA exhibits promising potential as an inhibitor of QS systems, providing a potential solution to the emerging problem of bacterial resistance.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.

8R-methoxy-9R-hydroxyl-fumitremorgin C, a new diketopiperazine alkaloid from Haima cold seep-derived fungus Aspergillus fumigatus CYH-5.

One novel diketopiperazine derivative 8R-methoxy-9R-hydroxyl-fumitremorgin C (1), together with twelve known compounds, was separated from the fungus Aspergillus fumigatus CYH-5 collected from Haima cold seep. The structures of the compounds were identified by NMR, MS, optical rotation, hydrolysis reaction and comparing with literatures. Among them, compounds 10 and 11 exhibited inhibitory effect against bacteria. Compound 11 showed inhibitory activity on α-glucosidase and compound 8 displayed acetylcholinesterase (AchE) inhibitory activity.

Indole diketopiperazine alkaloids and aromatic polyketides from the Antarctic fungus Penicillium sp. SCSIO 05705.

A new indole diketopiperazine alkaloid, named penilline D (1), together with five known indole alkaloid analogues (2-5, 11), two meroterpenoids (6 and 12), and four butenolide derivatives (7-10), were isolated from the Antarctic fungus Penicillium sp. SCSIO 05705. Extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation were used to elucidate the structure of penilline D (1), including its absolute configuration. All isolated compounds (1-12) were evaluated for their cytotoxic, antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among them, compound 5 exhibited moderate in vitro cytotoxic activity against the 143B cell line with IC50 value of 12.64 ± 0.78 µM. Compound 6 showed strong inhibitory activity against AChE with IC50 value of 0.36 nM (IC50 18.7 nM for Tacrine), while compounds 6 and 11 showed weak PL enzyme inhibitory activity. Furthermore, an in silico molecular docking study was also performed between 6 and AChE.

One new furanone analogue from the deep-sea fungus Purpureocillium sp. SCSIO 06693.

A new furanone analog, (E)-2-(8,9-dihydroxy-6,8-dimethyldec-4-en-2-yl)-met-hylfuran-3(2H)-one (1), together with six known compounds, including two diterpenoids (2 and 3), one butyrolactone (4) and three isocoumarins (5-7), were isolated from a deep-sea fungus, Purpureocillium sp. SCSIO 06693. Among them, compound 1 existed as two tautomeric forms (1a and 1b) differing in configuration of the furan ring. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Isolated compounds were evaluated for their cytotoxic, antiviral, antibacterial, antioxidant, acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Biological evaluation results revealed that compound 4 showed modest antioxidant activity against DPPH with IC50 value of 72.03 µM. In addition, compounds 1-4 exhibited PL enzyme inhibitory activities.

Diverse Secondary Metabolites from the Coral-Derived Fungus Aspergillus hiratsukae SCSIO 5Bn1003.

Three new metabolites, including a cyclic tetrapeptide asperhiratide (1), an ecdysteroid derivative asperhiratine (2), and a sesquiterpene lactone asperhiratone (3), were isolated and identified from the soft coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn1003, together with 10 known compounds. Their structures were elucidated via spectroscopic analysis, X-ray diffraction analysis, and electronic circular dichroism calculations. In addition, the absolute configuration of 1 was determined by Marfey's technique and an analysis of the acid hydrolysates using a chiral phase HPLC column. Among all the compounds, 6 and 8 showed medium cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), with IC50 values ranging from 31.03 ± 3.04 to 50.25 ± 0.54 µM. Meanwhile, they strongly inhibited α-glucosidase activities, with IC50 values of 35.73 ± 3.94 and 22.00 ± 2.45 µM, which were close to and even stronger than the positive control acarbose (IC50 = 32.92 ± 1.03 µM). Compounds 6-8 showed significant antibacterial activities against Bacillus subtilis, with MIC values of 10.26 ± 0.76 µM, 17.00 ± 1.25 µM, and 5.30 ± 0.29 µM, respectively. Compounds 9 and 12 exhibited potent radical scavenging activities against DPPH, with IC50 values of 12.23 ± 0.78 µM and 7.38 ± 1.16 µM. In addition, asperhiratide (1) was evaluated for anti-angiogenic activities in the in vivo zebrafish model, which showed a weak inhibitory effect on intersegmental vessel (ISV) formation.

Chevalones H-M: Six New α-Pyrone Meroterpenoids from the Gorgonian Coral-Derived Fungus Aspergillus hiratsukae SCSIO 7S2001.

Six new α-pyrone meroterpenoid chevalones H-M (1-6), together with six known compounds (7-12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1-5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25-100 µg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC50 values of 12.75, 9.29, and 20.11 µM, respectively.

Structurally Diverse Polycyclic Salicylaldehyde Derivative Enantiomers from a Marine-Derived Fungus Eurotium sp. SCSIO F452.

To enlarge the chemical diversity of Eurotium sp. SCSIO F452, a talented marine-derived fungus, we further investigated its chemical constituents from a large-scale fermentation with modified culture. Four pairs of new salicylaldehyde derivative enantiomers, euroticins F-I (1-4), as well as a known one eurotirumin (5) were isolated and characterized. Compound 1 features an unprecedented constructed 6/6/6/5 tetracyclic structures, while 2 and 3 represent two new types of 6/6/5 scaffolds. Their structures were established by comprehensive spectroscopic analyses, X-ray diffraction, 13C NMR, and electronic circular dichroism calculations. Selected compounds showed significant inhibitory activity against α-glucosidase and moderate cytotoxic activities against SF-268, MCF-7, HepG2, and A549 cell lines.

Asperorydines N-P, three new cyclopiazonic acid alkaloids from the marine-derived fungus Aspergillus flavus SCSIO F025.

Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.

Salicylaldehyde derivatives from a marine-derived fungus Eurotium sp. SCSIO F452.

Two pairs of new salicylaldehyde derivative enantiomers, salicylaldehydiums A and B (1 and 2), along with five known analogues were isolated and identified from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures and absolute configuration were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All the new optical pure enantiomers [(+)-1, (-)-1, (+)-2, (-)-2] were evaluated for their cytotoxic and antioxidative activities. Compound (-)-1 exhibited weak cytotoxic activity.

Euroticins A and B, Two Pairs of Highly Constructed Salicylaldehyde Derivative Enantiomers from a Marine-Derived Fungus Eurotium sp. SCSIO F452.

Two pairs of salicylaldehyde derivative enantiomers, euroticins A and B (1 and 2), were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Compound 1 possesses a highly constructed 6/6/6/5/7 pentacyclic structure featuring an unprecedented 2,11-dioxatricyclo[5.3.1.04,8]undecane core. Compound 2 represents the first example of 6/6/6/6 tetracyclic salicylaldehyde derivative. Their structures were established by spectroscopic analyses, X-ray diffraction, and electronic circular dichroism (ECD) and 13C NMR calculations. Compounds (+)-2 and (-)-2 exhibited remarkable antioxidative activities.

Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007.

Three new compounds, including two new 3,4,6-trisubstituted α-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), α-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 µg/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.

A new butenolide derivative from the deep-sea fungus Aspergillus terreus SCSIO FZQ028.

A new butenolide derivative (±)-asperteretal F (1) and related congener (2) recently reported containing an unusual 2-benzyl-3-phenyl substituted lactone core, together with five known compounds (3-7) were isolated and characterized from the fungus Aspergillus terreus. SCSIO FZQ028 derived from a deep-sea sediment of South China Sea. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, and HR-ESI-MS analysis. Additionally, all the compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against two tumor cell lines (SF-268 and HepG-2), and antimicrobial activities. Compounds 2-4, and 7 showed significant activities against DPPH with IC50 ranging from 5.89 to 10.07 µg/mL. Compounds 2 and 4 showed moderate antimicrobial activities against all four tested bacteria.[Figure: see text].

Three Pairs of New Spirocyclic Alkaloid Enantiomers From the Marine-Derived Fungus Eurotium sp. SCSIO F452.

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A-C (1-3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two "meta" products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were "ortho" products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.

Rubrobacter indicoceani sp. nov., a new marine actinobacterium isolated from Indian Ocean sediment.

A novel mesophilic marine actinobacterial strain, designated as SCSIO 08198T, was isolated from a deep-sea sediment sample collected from the Indian Ocean. The strain was Gram-stain-positive, rod-shaped and salmon pink in colour. Good growth occurred on marine agar with 1-5 % (w/v) NaCl and incubation at 28 °C for more than a fortnight. Sensitive to short ultraviolet radiation. Analysis of 16S rRNA gene sequences revealed that strain SCSIO 08198T had the highest similarity of 97.2 % to Rubrobacter radiotolerans DSM 5868T, and loosely related (<94.2 %) to all other species in the genus Rubrobacter. Phylogenetic analysis based on nearly complete 16S rRNA gene sequences revealed that the novel isolate shared a lineage with members of the genus Rubrobacter. The total cellular fatty acid profile was dominated by C16 : 0 12-methyl. MK-8 was the main menaquinone. The peptidoglycan type was A3α (l-Lys-l-Ala). The major phospholipids were diphosphatidylglycerol, phosphatidylglycerol and unidentified phospholipids. Based on the whole genome sequence analysis, the genome size is 3 078 689 bp with DNA G+C value of 63.8 mol%, including one circular chromosome and two plasmids. Based on these polyphasic data, a new species, Rubrobacterindicoceani sp. nov., is proposed, with the type strain SCSIO 08198T (=DSM 105148T=CGMCC 1.16398T).

Variecolortins A-C, Three Pairs of Spirocyclic Diketopiperazine Enantiomers from the Marine-Derived Fungus Eurotium sp. SCSIO F452.

Three pairs of spirocyclic diketopiperazine enantiomers, variecolortins A-C (1-3), were isolated from marine-derived fungus Eurotium sp. SCSIO F452. Compound 1 possesses an unprecedented highly functionalized seco-anthronopyranoid carbon skeleton featuring a 2-oxa-7-azabicyclo[3.2.1]octane core. Compounds 2 and 3 represent rare examples of a 6/6/6/6 tetracyclic cyclohexene-anthrone carbon scaffold. Their structures were determined by spectroscopic analyses, X-ray diffraction, and ECD calculations. Their enantiomers exhibited different antioxidative and cytotoxic activities, and their modes of action were investigated.

Eurotiumins A⁻E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452.

Three new prenylated indole 2,5-diketopiperazine alkaloids (1⁻3) with nine known ones (5⁻13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.

New chlorinated diphenyl ethers and xanthones from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001.

Seven new compounds, including four new chlorinated diphenyl ethers, namely chrysines A-D (1-4), one new dichlorinated xanthone, chrysoxanthone (5), dichloroorcinol (6), and one new benzeneacetic acid derivative, 3-isopentyl-4-hydroxy phenylacetic acid methyl ester (7), along with fourteen known compounds (8-21), were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures were determined by extensive spectroscopic methods and X-ray single-crystal diffraction analysis. All of the isolated compounds (1-21) were evaluated for their α-glucosidase inhibitory activity using PNPG method. Among them, nine compounds (2, 3, 5, 6, 8, 9, 13, 17, and 18) exhibited inhibitory activity against α-glucosidase with IC50 values of 0.35, 0.20, 0.04, 0.16, 0.15, 0.09, 0.14, 0.14, and 0.12mM, respectively (IC50 0.28mM for the positive control acarbose).

Antifungal New Oxepine-Containing Alkaloids and Xanthones from the Deep-Sea-Derived Fungus Aspergillus versicolor SCSIO 05879.

Phytopathogenic fungi remain a continuous and huge threat in the agricultural fields. The agrochemical industry has made great development of the use of microbial natural products, which has been regarded as an effective strategy against phytopathogenic fungi. Antifungal bioassay-directed fractionation was used to isolate two new oxepine-containing alkaloids (1 and 2), two new 4-aryl-quinolin-2-one alkaloids (3 and 4), and four new prenylated xanthones (5-8) from the deep-sea-derived fungus Aspergillus versicolor SCSIO 05879. Extensive NMR spectroscopic analysis, quantum mechanical calculations, and X-ray single-crystal diffraction were used to elucidate their structures, including their absolute configurations. Versicoloids A and B, versicone A, and cottoquinazoline A showed antifungal activities against three phytopathogenic fungi. The antifungal activities of these bioactive compounds strongly depend on the fungal species. Especially versicoloids A and B showed strong fungicidal effect (MIC of 1.6 µg/mL) against Colletotrichum acutatum, compared with that of the positive control cycloheximide (MIC of 6.4 µg/mL). The results of antifungal experiments indicated that versicoloids A and B may be regarded as candidate agents of antifungal agrochemicals.

Antiviral Merosesquiterpenoids Produced by the Antarctic Fungus Aspergillus ochraceopetaliformis SCSIO 05702.

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A-E (1-5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A-D (1-4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50 values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 µM, respectively. A possible biosynthetic pathway for ochraceopones A-E (1-5) was proposed.