RESUMEN
Seven previously undescribed compounds, including four diketomorpholine alkaloids (1â4), one indole diketopiperazine alkaloid (9), one chromone (10), and one benzoic acid derivative (13), and nine known compounds (5-8, 11, 12, and 14-16) were isolated from two different fungal sources. Nine of these metabolites (1-9) were obtained from a seagrass-derived Aspergillus alabamensis SYSU-6778, while the others were obtained from a mixed culture of A. alabamensis SYSU-6778 and a co-isolated fungus A. fumigatiaffinis SYSU-6786. The chemical structures of the compounds were deduced via spectroscopic techniques (including HRESIMS, 1D and 2D NMR), chemical reactions, and ECD calculations. It is worth noting that compound 10 was identified as a defensive secondary metabolite of strain SYSU-6786, produced through the induction of compound 8 under co-culture conditions. Compounds 3 and 4 possessed a naturally rare isotryptophan core. Moreover, compounds 1 and 2 exhibited potent inhibitory activities against fish pathogenic bacterium Edwardsiella ictalurid, with minimum inhibitory concentration values of 10.0 µg/mL for both compounds.
Asunto(s)
Aspergillus , Pruebas de Sensibilidad Microbiana , Aspergillus/química , Aspergillus/metabolismo , Estructura Molecular , Técnicas de Cocultivo , Metabolismo Secundario , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/biosíntesis , Antibacterianos/metabolismo , Animales , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/metabolismo , Dicetopiperazinas/química , Dicetopiperazinas/farmacología , Dicetopiperazinas/metabolismo , Dicetopiperazinas/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a DrogaRESUMEN
Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.
Asunto(s)
Plaquetas , Células Endoteliales de la Vena Umbilical Humana , Sepsis , Factor de von Willebrand , Animales , Sepsis/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Humanos , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inhibidores , Permeabilidad Capilar/efectos de los fármacosRESUMEN
Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (-)-nigrosporine C (-)-3, together with eight known compounds (4-11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1-3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher's method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 µmol/L and without cytotoxicity in a concentration of 100.0 µmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 µmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 µmol/L.
Asunto(s)
Alcaloides , Ascomicetos , Inhibidores de la Colinesterasa , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Animales , Ratones , Ascomicetos/química , Línea Celular , Óxido Nítrico/metabolismo , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Estructura Molecular , Acetilcolinesterasa/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Lipopolisacáridos/farmacologíaRESUMEN
Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37â°C (optimum, 28â°C), and in the presence of 0-10â% NaCl (w/v; optimum 3â%). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10â%) in both strains were iso-C15â:â0, iso-C15â:â1 G, and iso-C17â:â0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10âmol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83â%), followed by Flagellimonas aurea BC31-1-A7T (98.62â%), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76â%) and F. aurea BC31-1-A7T (98.55â%). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).
Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Filogenia , ARN Ribosómico 16S , Agua de Mar , Análisis de Secuencia de ADN , Vitamina K 2 , China , ARN Ribosómico 16S/genética , Sedimentos Geológicos/microbiología , Ácidos Grasos/análisis , Agua de Mar/microbiología , ADN Bacteriano/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análisis , Fosfatidiletanolaminas , Datos de Secuencia MolecularRESUMEN
Glioma is a clinically heterogeneous type of brain tumor with a poor prognosis. Current treatment approaches have limited effectiveness in treating glioma, highlighting the need for novel drugs. One approach is to explore marine natural products for their therapeutic potential. In this study, we isolated nine shikimate-derived diisoprenyl-cyclohexene/ane-type meroterpenoids (1-9), including four new ones, amphicordins A-D (1-4) from the ascidian-derived fungus Amphichorda felina SYSU-MS7908, and further semisynthesized four derivatives (10-13). Their structures were extensively characterized using 1D and 2D NMR, modified Mosher's method, HR-ESIMS, NMR and ECD calculations, and X-ray crystallography. Notably, amphicordin C (3) possesses a unique benzo[g]chromene (6/6/6) skeleton in this meroterpenoid family. In an anti-glioma assay, oxirapentyn A (7) effectively inhibited the proliferation, migration, and invasion of glioma cells and induced their apoptosis. Furthermore, an in silico analysis suggested that oxirapentyn A has the potential to penetrate the blood-brain barrier. These findings highlight the potential of oxirapentyn A as a candidate for the development of novel anti-glioma drugs.
Asunto(s)
Beauveria , Glioma , Urocordados , Animales , Humanos , Ácido Shikímico , Glioma/tratamiento farmacológico , Estructura MolecularRESUMEN
A Gram-stain-negative, aerobic, motile, ovoid-shaped and yellow-coloured strain, designated SYSU M79828T, was isolated from seawater collected from the South China Sea. Growth of this strain was observed at 4-37 °C (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-6% NaCl (optimum, 3.0â%, w/v). The respiratory quinone was found to be Q-10. Major fatty acid constituents were C18â:â1 ω7c/C18â:â1 ω6c, C18â:â1 ω7c11-methyl and C18â:â0 (>5â% of total). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, two unidentified phospholipid, one unidentified lipid and an unidentified glycolipid. The genomic DNA G+C content was 64.5âmol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M79828T belonged to the genus Cereibacter and had the highest sequences similarity to 'Rhodobacter xinxiangensis' TJ48T (98.41â%). Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterizations, we consider that strain SYSU M79828T represents a novel species of the genus Cereibacter, for which the name Cereibacter flavus sp. nov. is proposed. The type strain is SYSU M79828T (=GDMCC 1.3803T=KCTC 92893T). In addition, according to the results of phylogenetic analysis and similar taxonomic characteristics, we propose that Rhodobacter alkalitolerans should be reclassified as Cereibacter alkalitolerans comb. nov.
Asunto(s)
Ácidos Grasos , Rhodobacteraceae , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Rhodobacter , Agua de Mar , ChinaRESUMEN
Understanding the biosynthetic pathways of fungal pigments can help elucidate their roles in fungal growth processes. Trichodimerol is a unique cage-like dimeric sorbicillinoids pigment that is commonly isolated from many fungi, however, its biosynthesis is just partially clarified. In this study, we report that a biosynthetic gene cluster encoded major facilitator superfamily transporter (StaE) from the fungus Stagonospora sp. SYSU-MS7888 is involved in the formation of trichodimerol, together with several other dimeric sorbicillinoids. Using Aspergillus oryzae NSARI as a heterologous host, we demonstrated that the formation of dimeric sorbicillinoids required co-expression of the transporter StaE with biosynthetic genes (two PKSs and one monooxygenase) that are responsible for constructing the monomer precursor sorbicillinol. Fluorescence microscopy results showed that eGFP-tagged StaE is localized on the endoplasmic reticulum, suggesting that sorbicillinoid dimerizations might be compartmentalized in this organelle.
Asunto(s)
Ascomicetos , Dimerización , Familia de MultigenesRESUMEN
A combination strategy of 13C NMR and bioinformatics was established to expedite the discovery of acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. This approach led to the identification of 13 acetylenic meroterpenoids (1-13) and four biogenic analogs (14-17), including five new ones named felinoids A-E (1-4 and 15). Their structures and absolute configurations were elucidated using extensive spectroscopy, ECD quantum chemical calculations, and single-crystal X-ray diffraction analysis. Compound 1 possessed a rare cyclic carbonate in natural acetylenic meroterpenoids. The plausible shikimate-terpenoid biosynthetic pathways of 1-4 were also postulated. Five of these isolates exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 cells (IC50 = 11.6-19.5 µM). Moreover, oxirapentyn E diacetate showed a dose-dependent inhibition of pro-inflammatory cytokines IL-6 and TNF-α. Structural modification of oxirapentyn B yielded 29 new derivatives, among which seven showed improved activity (IC50 < 3 µM) and higher selectivity index (SI > 22). The structure-activity relationship study indicated that 7, 8-epoxy, and 6-acylation were crucial for the activity. These findings may provide a powerful tool to accelerate the discovery of new fungal acetylenic meroterpenoids for future anti-inflammatory drug development.
Asunto(s)
Acetileno , Urocordados , Animales , Estructura Molecular , Alquinos , Terpenos/química , Antiinflamatorios/química , Espectroscopía de Resonancia Magnética , HongosRESUMEN
Sour rot, caused by Geotrichum citri-aurantii, is a major postharvest disease in citrus and results in significant economic losses. The genus Beauveria is recognized as a promising source of biocontrol agents for agricultural applications. Herein, we established a targeted strategy by integrating genomics and metabolomics to accelerate the discovery of new cyclopeptides from antagonistic metabolites produced by the marine-derived fungus Beauveria felina SYSU-MS7908. As a result, we isolated and characterized seven cyclopeptides, including six new molecules, isaridins I-N (1-6). Their chemical structures and conformational analysis were extensively elucidated using spectroscopic techniques (NMR, HRMS, and MS'MS data), modified Mosher's and Marfey's methods, and single-crystal X-ray diffraction. Notably, isaridin K (3) contains a peptide backbone with an N-methyl-2-aminobutyric acid residue rarely found in natural cyclopeptides. Bioassays showed that compound 2 could significantly inhibit the mycelial growth of G. citri-aurantii by destroying the cell membrane. These findings provide an effective strategy for searching for new fungal peptides for potential agrochemical fungicides and also pave the way for further exploration of applications in agriculture, food, and medicine.
Asunto(s)
Beauveria , Citrus , Antifúngicos/farmacología , Beauveria/química , Péptidos Cíclicos/farmacología , Metabolómica , Citrus/microbiologíaRESUMEN
Two new cyclopropane derivatives (1-2) and seven undescribed α-pyrone derivatives (3-9), along with one known congener (10) were obtained from the marine fungus Stagonospora sp. SYSU-MS7888, which was isolated from the South China Sea. Their planar structures were established through extensive spectroscopic analyses including 1D and 2D NMR and HR-ESIMS. The absolute configurations were identified on basis of the quantum chemical calculations of ECD and NMR, as well as the modified Mosher's method. It's particularly noteworthy that the tetrasubstituted furopyrans, chenopodolans A-F, possessing phytotoxicity and zootoxicity, were structural misassignments. The structures of chenopodolans featuring with furopyran skeleton were revised as common trisubstituted α-pyrones by computational chemistry, NMR spectroscopic method, and empirical rule. Compounds 1, 2, 7, and 9 showed significant anti-inflammatory activity with IC50 values ranging from 3.6 to 22.8 µM, which is better than the positive control indomethacin (IC50 = 26.5 ± 1.13 µM). This discovery holds potential for the development of new anti-inflammatory agents.
Asunto(s)
Ascomicetos , Pironas , Pironas/farmacología , Pironas/química , Estructura Molecular , Ascomicetos/química , Espectroscopía de Resonancia Magnética , Antiinflamatorios , CiclopropanosRESUMEN
An effective identification and discovery of fungal pigments is very important to illustrate the role of fungal pigments in the life process and conduce to the discovery of new bioactive and edible pigments. The phenotype combined with metabolomic and genomic (PMG) strategy led to the discovery and characterization of three new sorbicillinoid pigments, stasorbicillinoids A-C (1-3), and five known analogues (4-8) from the sponge-derived fungus Stagonospora sp. SYSU-MS7888. Their structures were elucidated by the application of spectroscopic methods (NMR, MS, UV, IR, and ECD) and modified Mosher's method. Compounds 1 and 2 featured novel naphthone nuclei linked by two alkyl side chains possibly undergoing inter- and intramolecular Michael reactions. Compounds 1-8 exhibited potent anti-inflammatory activity with IC50 values in the range of 3.56-22.8 µM. Furthermore, compound 2 inhibited the production of IL-1ß, IL-6, and TNF-α in a dose-dependent manner. This study provides an effective strategy to accelerate the discovery of new fungal pigments and further exploration of their potential applications in different fields such as medicine and food industries.
Asunto(s)
Genómica , Metabolómica , Antiinflamatorios/farmacologíaRESUMEN
There has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered, while new monoterpenes were rarely isolated from marine-derived fungi in the past two decades. Three new monoterpenes, diaporterpenes A-C (1-3), and one new α-pyrones, diaporpyrone A (6), along with nine known polyketides 4, 5, and 7-13 were isolated from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR and HR-ESIMS). The absolute configurations of 1 and 3 were identified by an X-ray crystallographic diffraction experiment using Cu-Ka radiation, and those of compound 2 were assigned by calculating NMR chemical shifts and ECD spectra. It afforded an example of natural epimers with different physical properties, especially crystallization, due to the difference in intermolecular hydrogen bonding. Compounds 9, 10, and 13 showed moderate total antioxidant capacity (0.82 of 9; 0.70 of 10; 0.48 of 13) with Trolox (total antioxidant capacity: 1.0) as a positive control, and compounds 5 and 7 showed anti-inflammatory activity with IC50 values of 35.4 and 40.8 µM, respectively (positive control indomethacin: IC50 = 35.8 µM).
Asunto(s)
Policétidos , Urocordados , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Hongos/química , Indometacina , Estructura Molecular , Monoterpenos , Policétidos/química , Pironas/químicaRESUMEN
Culturing ascidian-derived fungus Amphichorda felina SYSU-MS7908 under standard laboratory conditions mainly yielded meroterpenoid, and nonribosomal peptide-type natural products. We sequenced the genome of Amphichorda felina SYSU-MS7908 and found 56 biosynthetic gene clusters (BGCs) after bioinformatics analysis, suggesting that the majority of those BGCSs are silent. Here we report our genome mining effort on one cryptic BGC by heterologous expression in Aspergillus oryzae NSAR1, and the identification of two new α-pyrone derivatives, amphichopyrone A (1) and B (2), along with a known compound, udagawanone A (3). Anti-inflammatory activities were performed, and amphichopyrone A (1) and B (2) displayed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production in RAW264.7 cells with IC50 values 18.09 ± 4.83 and 7.18 ± 0.93 µM, respectively.
Asunto(s)
Beauveria , Productos Biológicos , Urocordados , Animales , Beauveria/metabolismo , Productos Biológicos/metabolismo , Productos Biológicos/farmacología , Pironas/farmacología , Urocordados/genética , Urocordados/metabolismoRESUMEN
Fungal cytochrome P450 enzymes have been shown to catalyze regio- and stereoselective oxidative intermolecular phenol coupling. However, an enzyme capable of catalyzing undirected para-para (C4-4') coupling has not been reported. Here, we revealed the biosynthetic gene cluster (BGC) of phomoxanthone A from the marine fungus Diaporthe sp. SYSU-MS4722. We heterologously expressed 14 biosynthetic genes in Aspergillus oryzae NSAR1 and found that PhoCDEFGHK is involved in the early stage of phomoxanthone A biosynthesis to give chrysophanol and that chrysophanol is then processed by PhoBJKLMNP to yield penexanthone B. A feeding experiment suggested that PhoO, a cytochrome P450 enzyme, catalyzed the regioselective oxidative para-para coupling of penexanthone B to give phomoxanthone A. The mechanism of PhoO represents a novel enzymatic 4,4'-linkage dimerization method for tetrahydroxanthone formations, which would facilitate biosynthetic engineering of structurally diverse 4,4'-linked dimeric tetrahydroxanthones.
Asunto(s)
Vías Biosintéticas , Fenol , Sistema Enzimático del Citocromo P-450/metabolismo , Fenoles/metabolismo , XantonasRESUMEN
Seven new xanthones, diaporthones A-G (1-7), together with 13 known analogues, including five mono- (8-14) and six dimeric xanthones (15-20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1-7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15-20 showed significant anti-inflammatory activity with IC50 values between 6.3 and 8.0 µM. In addition, dimeric xanthones (15-20) showed selective cytotoxicity against T98G cell lines with IC50 values ranging from 19.5 to 78.0 µM.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Hongos , Urocordados , Xantonas/farmacología , Animales , Antiinflamatorios/química , Antineoplásicos/química , Organismos Acuáticos , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Glioma/patología , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Ratones , Células RAW 264.7 , Relación Estructura-Actividad , Xantonas/químicaRESUMEN
Covering 1989 to 2020The mangrove forests are a complex ecosystem occurring at tropical and subtropical intertidal estuarine zones and nourish a diverse group of microorganisms including fungi, actinomycetes, bacteria, cyanobacteria, algae, and protozoa. Among the mangrove microbial community, mangrove associated fungi, as the second-largest ecological group of the marine fungi, not only play an essential role in creating and maintaining this biosphere but also represent a rich source of structurally unique and diverse bioactive secondary metabolites, attracting significant attention of organic chemists and pharmacologists. This review summarizes the discovery relating to the source and characteristics of metabolic products isolated from mangrove-associated fungi over the past thirty years (1989-2020). Its emphasis included 1387 new metabolites from 451 papers, focusing on bioactivity and the unique chemical diversity of these natural products.
Asunto(s)
Actinobacteria , Productos Biológicos , Cianobacterias , Productos Biológicos/química , Cianobacterias/química , Ecosistema , Hongos/metabolismoRESUMEN
BACKGROUND: This study aimed to investigate the influence of extrauterine growth restriction (EUGR) on pulmonary arterial pressure (PAP) and the transgenerational inheritance of promoter methylation changes in pulmonary vascular endothelial cells (PVECs) of 2 consecutive generations under EUGR stress. METHODS: After modeling, PAP values of F1 and F2 pups were investigated at 9-week-old. The methyl-DNA immune precipitation chip was used to analyze DNA methylation profiling. Differential enrichment peaks (DEPs) and regions of interest (ROIs) were identified, based on which Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and reactome pathway enrichments were analyzed. RESULTS: The F1 male rats in the EUGR group had significantly increased PAP levels compared to the control group; however, this increase was not observed in female rats. Interestingly, in F2 female rats, the EUGR group had decreased PAP. In the X chromosome of the F1 males, there were 16 differential ROI genes in the F1 generation, while in F2 females, there were 86 differential ROI genes. Similarly, there were 105 DEPs in the F1 generation and 38 DEPs in the F2 generation. In combination with the 5 common ROIs and 14 common DEPs, 18 genes were regarded as the key candidate genes associated with hereditable PAP variation in the EUGR model. Enrichment analysis showed that synaptic and neurotransmitter relative pathways might be involved in the process of EUGR-induced PAH development. Among common DEPs, Smad1 and Serpine1 were also found in 102 PAH-associated genes in the MalaCards database. CONCLUSIONS: Together, there is a transgenerational inheritance of promoter methylation changes in the X chromosome in EUGR-induced PAP disorders, which involves the participation of synaptic and neurotransmitter relative pathways. Also, attenuated methylation of Smad1 and Serpine1 in the promoter region may be a partial driver of PAH in later life.
RESUMEN
Under guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A-J (1-10) along with two known analogues (11 and 12), were isolated from the marine-derived fungusFusarium decemcellulare SYSU-MS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J-based configurational analysis (JBCA), chemical degradation, geminal proton rule, and the modified Mosher's method were adopted to fix their absolute configurations in the side chain. Compounds 3 and 10 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50values 22.4 ± 1.8 and 21.7 ± 1.1 µM. In addition, compounds 3 and 10 displayed MptpA inhibitory activity with an IC50 value of 19.2 ± 0.9 and 33.1 ± 2.9 µM. Structure-activity relationships of the polypropionate derivatives were discussed.
Asunto(s)
Antiinflamatorios/química , Propionatos/química , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Fusarium/química , Fusarium/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Óxido Nítrico/metabolismo , Propionatos/aislamiento & purificación , Propionatos/farmacología , Proteínas Tirosina Fosfatasas/metabolismo , Células RAW 264.7RESUMEN
Six new fusarin derivatives, fusarins G-L (1-6), together with five known compounds (5-11) were isolated from the marine-derived fungus Fusarium solani 7227. The structures of the new compounds were elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS, ECD, and ORC) and X-ray crystallography. Compounds 5-11 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide, with IC50 values ranging from 3.6 to 32.2 µM. The structure-activity relationships of the fusarins are discussed herein.
Asunto(s)
Antiinflamatorios/farmacología , Fusarium , Lactamas/farmacología , Óxido Nítrico/antagonistas & inhibidores , Polienos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Fermentación , Fusarium/química , Fusarium/metabolismo , Lactamas/aislamiento & purificación , Lipopolisacáridos/farmacología , Ratones , Óxido Nítrico/metabolismo , Polienos/aislamiento & purificación , Células RAW 264.7 , Metabolismo Secundario , Relación Estructura-ActividadRESUMEN
Ascidian-derived microorganisms are a significant source of pharmacologically active metabolites with interesting structural properties. When discovering bioactive molecules from ascidian-derived fungi, two new phenols, roussoelins A (1) and B (2), and ten known polyketides (3-12) were isolated from the ascidian-derived fungus Roussoella siamensis SYSU-MS4723. The planar structure of compounds 1 and 2 was established by analysis of HR-ESIMS and NMR data. The conformational analysis of the new compounds was assigned according to coupling constants and selective gradient NOESY experiments, and absolute configurations were completed by the modified Mosher's method. Among the isolated compounds, 1, 2, and 9 showed moderate antioxidant capacity.