Metabolites with Anti-Inflammatory Activity from the Mangrove Endophytic Fungus Diaporthe sp. QYM12

One new diterpenoid, diaporpenoid A (1), two new sesquiterpenoids, diaporpenoids B–C (2,3) and three new α-pyrone derivatives, diaporpyrones A–C (4–6) were isolated from an MeOH extract obtained from cultures of the mangrove endophytic fungus Diaporthe sp. QYM12. Their structures were elucidated by extensive analysis of spectroscopic data. The absolute configurations were determined by electronic circular dichroism (ECD) calculations and a comparison of the specific rotation. Compound 1 had an unusual 5/10/5-fused tricyclic ring system. Compounds 1 and 4 showed potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC₅₀ values of 21.5 and 12.5 μM, respectively.     

Bioactive Chaetoglobosins from the Mangrove Endophytic Fungus Penicillium chrysogenum

A novel chaetoglobosin named penochalasin I (1) with a unprecedented six-cyclic 6/5/6/5/6/13 fused ring system, and another new chaetoglobosin named penochalasin J (2), along with chaetoglobosins G, F, C, A, E, armochaetoglobosin I, and cytoglobosin C (3–9) were isolated from the culture of Penicillium chrysogenum V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and high resolution mass spectroscopic data. The absolute configuration of compounds 1 and 2 were determined by comparing the theoretical electronic circular dichroism (ECD) calculation with the experimental CD. Compound 1 was the first example, with a six-cyclic fused ring system formed by the connection of C-5 and C-2′ of the chaetoglobosin class. Compounds 5–8 remarkably inhibited the plant pathogenic fungus R. solani (minimum inhibitory concentrations (MICs) = 11.79–23.66 μM), and compounds 2, 6, and 7 greatly inhibited C. gloeosporioides (MICs = 23.58–47.35 μM), showing an antifungal activity higher than that of carbendazim. Compound 1 exhibited marked cytotoxicity against MDA-MB-435 and SGC-7901 cells (IC₅₀ < 10 μM), and compounds 6 and 9 showed potent cytotoxicity against SGC-7901 and A549 cells (IC₅₀ < 10 μM).     

Polyketide Derivatives,Guhypoxylonols A–D from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y45 That Inhibit Nitric Oxide Production

Four undescribed compounds, guhypoxylonols A (1), B (2), C (3), and D (4), were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y45, together with seven previously reported metabolites. The structures of 1–4 were elucidated based on analysis of HRESIMS and NMR spectroscopic data. The absolute configurations of the stereogenic carbons in 1–3 were established through a combination of spectroscopic data and electronic circular dichroism (ECD). Compounds 1–11 were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4, and 6 showed an inhibitory activity against the production of nitric oxide (NO), with the IC₅₀ values of 14.42 ± 0.11, 18.03 ± 0.14, 16.66 ± 0.21, and 21.05 ± 0.13 μM, respectively.     

Isolation,Structural Characterization and Antidiabetic Activity of New Diketopiperazine Alkaloids from Mangrove Endophytic Fungus Aspergillus sp. 16-5c

Six new DIKETOPIPERAZINE alkaloids aspergiamides A–F (1–6), together with ten known alkaloids (7–16), were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5c. The structures of the new compounds were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of aspergiamides A-F were established based on the experimental and calculated ECD data. All the compounds were evaluated for the antidiabetic activity against α-glucosidase and PTP1B enzyme. The bioassay results disclosed compounds 1 and 9 exhibited significant α-glucosidase inhibitory with IC₅₀ values of 18.2 and 7.6 μM, respectively; compounds 3, 10, 11, and 15 exhibited moderate α-glucosidase inhibition with IC₅₀ values ranging from 40.7 to 83.9 μM; while no compounds showed obvious PTP1B enzyme inhibition activity.     

Three New Resveratrol Derivatives from the Mangrove Endophytic Fungus Alternaria sp.

Three new resveratrol derivatives, namely, resveratrodehydes A–C (1–3), were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC₅₀ < 50 μM). Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC₅₀ < 10 μM). Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay.     

Four New Chromones from the Endophytic Fungus Phomopsis asparagi DHS-48 Isolated from the Chinese Mangrove Plant Rhizophora mangle

Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher’s method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC₅₀ of 34 μM and 117 μM.     

Six New Polyketide Decalin Compounds from Mangrove Endophytic Fungus Penicillium aurantiogriseum 328#

Six new compounds with polyketide decalin ring, peaurantiogriseols A–F (1–6), along with two known compounds, aspermytin A (7), 1-propanone,3-hydroxy-1-(1,2,4a,5,6,7,8,8a-octahydro-2,5-dihydroxy-1,2,6-trimethyl-1-naphthalenyl) (8), were isolated from the fermentation products of mangrove endophytic fungus Penicillium aurantiogriseum 328#. Their structures were elucidated based on their structure analysis. The absolute configurations of compounds 1 and 2 were determined by ¹H NMR analysis of their Mosher esters; the absolute configurations of 3–6 were determined by using theoretical calculations of electronic circular dichroism (ECD). Compounds 1–8 showed low inhibitory activity against human aldose reductase, no activity of inducing neurite outgrowth, nor antimicrobial activity.     

New Meroterpenoids from the Endophytic Fungus Aspergillus flavipes AIL8 Derived from the Mangrove Plant Acanthus ilicifolius

Four new meroterpenoids (2–5), along with three known analogues (1, 6, and 7) were isolated from mangrove plant Acanthus ilicifolius derived endophytic fungus Aspergillus flavipes. The structures of these compounds were elucidated by NMR and MS analysis, the configurations were assigned by CD data, and the stereochemistry of 1 was confirmed by X-ray crystallography analysis. A possible biogenetic pathway of compounds 1–7 was also proposed. All compounds were evaluated for antibacterial and cytotoxic activities.     

Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3

Eight new compounds, including two sambutoxin derivatives (1–2), two highly oxygenated cyclopentenones (7–8), four highly oxygenated cyclohexenones (9–12), together with four known sambutoxin derivatives (3–6), were isolated from semimangrove endophytic fungus Talaromyces sp. CY-3, under the guidance of molecular networking. The structures of new isolates were elucidated by analysis of detailed spectroscopic data, ECD spectra, chemical hydrolysis, ¹³C NMR calculation, and DP4+ analysis. In bioassays, compounds 1–5 displayed better α-glucosidase inhibitory activity than the positive control 1-deoxynojirimycin (IC₅₀ = 80.8 ± 0.3 μM), and the IC₅₀ value was in the range of 12.6 ± 0.9 to 57.3 ± 1.3 μM.     

枇杷内生真菌中拮抗石榴干腐病菌菌株的筛选

采用对峙培养法,从97株枇杷内生真菌中,筛选对石榴干腐病病菌有拮抗活性的菌株。结果表明：97株真菌对石榴干腐病病菌均有一定的抑制效果,抑制率在70%以上的菌株有29个,60%～70%的菌株共33个,50%～60%的菌株共30个,50%以下的菌株5个。抑制率在50%以上的菌株共92株,占总数的94.8%,其中P3.9菌株的抑制效果最好,其抑制率达93%,表现出良好的开发前景。此结果为有效可持续防控石榴干腐病提供生防菌种资源。     

Secondary Metabolites of a Mangrove Endophytic Fungus Aspergillus terreus (No. GX7-3B) from the South China Sea

The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7), 3β,5α,14α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (8), NGA0187 (9) and beauvericin (10), were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE) with IC₅₀ values 2.01, 6.71, 1.89, and 3.09 μM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC₅₀ values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68 and 1.14 (Hela), and 1.50 and 1.10 μM (KB), respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them.     

Bioactive Metabolites from Mangrove Endophytic Fungus Aspergillus sp. 16-5B

Chemical investigation of the endophytic fungus Aspergillus sp. 16-5B cultured on Czapek’s medium led to the isolation of four new metabolites, aspergifuranone (1), isocoumarin derivatives (±) 2 and (±) 3, and (R)-3-demethylpurpurester A (4), together with the known purpurester B (5) and pestaphthalides A (6). Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The absolute configuration of Compound 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra, and that of Compound 4 was revealed by comparing its optical rotation data and CD with those of the literature. The structure of Compound 6 was further confirmed by single-crystal X-ray diffraction experiment using CuKα radiation. All isolated compounds were evaluated for their α-glucosidase inhibitory activities, and Compound 1 showed significant inhibitory activity with IC₅₀ value of 9.05 ± 0.60 μM. Kinetic analysis showed that Compound 1 was a noncompetitive inhibitor of α-glucosidase. Compounds 2 and 6 exhibited moderate inhibitory activities.     

Alterporriol-Type Dimers from the Mangrove Endophytic Fungus,Alternaria sp. (SK11), and Their MptpB Inhibitions

A new alterporriol-type anthranoid dimer, alterporriol S (1), along with seven known anthraquinone derivatives, (+)-aS-alterporriol C (2), hydroxybostrycin (3), halorosellinia A (4), tetrahydrobostrycin (5), 9α-hydroxydihydrodesoxybostrycin (6), austrocortinin (7) and 6-methylquinizarin (8), were isolated from the culture broth of the mangrove fungus, Alternaria sp. (SK11), from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods, including 1D and 2D NMR spectra. The absolute configurations of 1 and the axial configuration of 2 were defined by experimental and theoretical ECD spectroscopy. 1 was identified as the first member of alterporriols consisting of a unique C-10−C-2′ linkage. Atropisomer 2 exhibited strong inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with an IC₅₀ value 8.70 μM.     

Antimicrobial Meroterpenoids and Erythritol Derivatives Isolated from the Marine-Algal-Derived Endophytic Fungus Penicillium chrysogenum XNM-12

One new meroterpenoid-type alkaloid, oxalicine C (1), and two new erythritol derivatives, penicierythritols A (6) and B (7), together with four known meroterpenoids (2–5), were isolated from the marine algal-derived endophytic fungus Penicillium chrysogenum XNM-12. Their planar structures were determined by means of spectroscopic analyses, including UV, 1D and 2D NMR, and HRESIMS spectra. Their stereochemical configurations were established by comparing the experimental and calculated electronic circular dichroism (ECD) spectra for compound 1, as well as by comparison of the optical rotations with literature data for compounds 6 and 7. Notably, oxalicine C (1) represents the first example of an oxalicine alkaloid with a cleaved α-pyrone ring, whereas penicierythritols A (6) and B (7) are the first reported from the Penicillium species. The antimicrobial activities of compounds 1–7 were evaluated. Compounds 1 and 6 exhibited moderate antibacterial effects against the plant pathogen Ralstonia solanacearum with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL, respectively. Compound 6 also possesses moderate antifungal properties against the plant pathogen Alternaria alternata with a MIC value of 8 μg/mL.     

Three New Asperentin Derivatives from the Algicolous Fungus Aspergillus sp. F00785

Three new asperentin-type compounds, 6-O-α-d-ribosylasperentin (1) and 6-O-α-d-ribosyl-8-O-methylasperentin (2) and 5-hydroxyl-6-O-methylasperentin (3), along with asperentin (4) and its known analogues (5–9), were isolated from a halotolerant Aspergillus sp. strain {"type":"entrez-nucleotide","attrs":{"text":"F00785","term_id":"707638","term_text":"F00785"}}F00785, an endotrophic fungus from marine alga. Their structures were determined using extensive NMR and HRESIMS spectroscopic analysis, including the X-ray crystallographic data for the assignment of the absolute configurations of compound 9. Compound 4 exhibited highly potent inhibitory activity against crop pathogens, Colletotrichum gleosporioides Penz. and Colletotrichum gleosporioides (Penz.) Sacc.     

Identification and Bioactivity of Compounds from the Mangrove Endophytic Fungus Alternaria sp.

Racemic new cyclohexenone and cyclopentenone derivatives, (±)-(4R*,5S*,6S*)-3-amino-4,5,6-trihydroxy-2-methoxy-5-methyl-2-cyclohexen-1-one (1) and (±)-(4S*,5S*)-2,4,5-trihydroxy-3-methoxy-4-methoxycarbonyl-5-methyl-2-cyclopenten-1-one (2), and two new xanthone derivatives 4-chloro-1,5-dihydroxy-3-hydroxymethyl-6-methoxycarbonyl-xanthen-9-one (3) and 2,8-dimethoxy-1,6-dimethoxycarbonyl-xanthen-9-one (4), along with one known compound, fischexanthone (5), were isolated from the culture of the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS (Mass), one and two dimensional NMR (nuclear magnetic resonance) spectroscopic data. Compounds 1 and 2 exhibited potent ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] scavenging activities with EC₅₀ values of 8.19 ± 0.15 and 16.09 ± 0.01 μM, respectively. In comparison to Triadimefon, compounds 2 and 3 exhibited inhibitory activities against Fusarium graminearum with minimal inhibitory concentration (MIC) values of 215.52 and 107.14 μM, respectively, and compound 3 exhibited antifungal activity against Calletotrichum musae with MIC value of 214.29 μM.     

Thioester-Containing Benzoate Derivatives with α-Glucosidase Inhibitory Activity from the Deep-Sea-Derived Fungus Talaromyces indigoticus FS688

Eurothiocins C–H (1–6), six unusual thioester-containing benzoate derivatives, were isolated from the deep-sea-derived fungus Talaromyces indigoticus FS688 together with a known analogue eurothiocin A (7). Their structures were elucidated through spectroscopic analysis and the absolute configurations were determined by X-ray diffraction and ECD calculations. In addition, compound 1 exhibited significant inhibitory activity against α-glucosidase with an IC₅₀ value of 5.4 μM, while compounds 4 and 5 showed moderate effects with IC₅₀ values of 33.6 and 72.1 μM, respectively. A preliminary structure–activity relationship is discussed and a docking analysis was performed.     

New Polyketides from Mangrove Endophytic Fungus Penicillium sp. BJR-P2 and Their Anti-Inflammatory Activity

Four new polyketide compounds, including two new unique isocoumarins penicillol A (1) and penicillol B (2) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (3) and citreoviridin I (4), along with four known analogues were isolated from the mangrove endophytic fungus Penicillium sp. BJR-P2. Their structures were elucidated by extensive spectroscopic methods. The absolute configurations of compounds 1–4 based on electronic circular dichroism (ECD) calculations, DP4+ analysis, and single-crystal X-ray diffraction are presented. All the new compounds were evaluated for anti-inflammatory activity. An anti-inflammatory assay indicated that compound 2 inhibited lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC₅₀) values of 12 μM, being more potent than the positive control, indomethacin (IC₅₀ = 35.8 ± 5.7 μM). Docking study showed that compound 2 was perfectly docking into the active site of murine inducible nitric oxide oxygenase (iNOS) via forming multiple typical hydrogen bonds.     

Asperlones A and B,Dinaphthalenone Derivatives from a Mangrove Endophytic Fungus Aspergillus sp. 16-5C

Racemic dinaphthalenone derivatives, (±)-asperlone A (1) and (±)-asperlone B (2), and two new azaphilones, 6″-hydroxy-(R)-mitorubrinic acid (3) and purpurquinone D (4), along with four known compounds, (−)-mitorubrinic acid (5), (−)-mitorubrin (6), purpurquinone A (7) and orsellinic acid (8), were isolated from the cultures of Aspergillus sp. 16-5C. The structures were elucidated using comprehensive spectroscopic methods, including 1D and 2D NMR spectra and the structures of 1 further confirmed by single-crystal X-ray diffraction analysis, while the absolute configuration of 3 and 4 were determined by comparing their optical rotation and CD with those of the literature, respectively. Compounds 1, 2 and 6 exhibited potent inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with IC₅₀ values of 4.24 ± 0.41, 4.32 ± 0.60 and 3.99 ± 0.34 μM, respectively.     

Peniciadametizine A,a Dithiodiketopiperazine with a Unique Spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] Skeleton,and a Related Analogue,Peniciadametizine B,from the Marine Sponge-Derived Fungus Penicillium adametzioides

Peniciadametizine A (1); a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7''-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2); as well as two known compounds, brasiliamide A (3); and viridicatumtoxin (4), were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT) conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD) calculations. The spiro[furan-2,7''-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.