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1.
Molecules ; 29(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38731603

ABSTRACT

A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher's method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day.


Subject(s)
Alkaloids , Penicillium , Quinazolinones , Rhodiola , Seeds , Penicillium/chemistry , Quinazolinones/chemistry , Quinazolinones/pharmacology , Rhodiola/chemistry , Rhodiola/microbiology , Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , Germination/drug effects , Molecular Structure , Endophytes/chemistry
2.
Sci Rep ; 14(1): 11228, 2024 05 16.
Article in English | MEDLINE | ID: mdl-38755187

ABSTRACT

Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are becoming ineffective, and the situation worsens on a logarithmic scale. Novel antifungals from unique natural sources are highly sought to cope sustainably with the situation. Metabolites from endophytic microbes are the best-fitted alternatives in this case. Endophytes are the untapped sources of 'plants' internal microbial population' and are promising sources of effective bio-therapeutic agents. Fungal endophytes were isolated from Tropaeolum majus and checked for antifungal activity against selected plant and human pathogens. Bioactive metabolites were identified through chromatographic techniques. The mode of action of those metabolites was evaluated through various spectroscopic techniques. The production of antifungal metabolite was optimized also. In particular VOCs (volatile organic compounds) of TML9 were tested in vitro for their anti-phytopathogenic activity. Ethyl acetate (EA) extract of cell-free culture components of Colletotrichum aenigma TML3 exhibited broad-spectrum antifungal activity against four species of Candida and the major constituents reported were 6-pentyl-2H-pyran-2-one, 2-Nonanone, 1 propanol 2-amino. The volatile metabolites, trans-ocimene, geraniol, and 4-terpinyl acetate, produced from Curvularia lunata TML9, inhibited the growth of some selected phyto pathogens. EA extract hampered the biofilm formation, minimised the haemolytic effect, and blocked the transformation of Candida albicans (MTCC 4748) from yeast to hyphal form with a Minimum Fungicidal Concentration (MFC) of 200-600 µg mL-1. Central carbohydrate metabolism, ergosterol synthesis, and membrane permeability were adversely affected and caused the lethal leakage of necessary macromolecules of C. albicans. Volatile metabolites inhibited the growth of phytopathogens i.e., Rhizoctonia solani, Alternaria alternata, Botrytis cinerea, Cercospora beticola, Penicillium digitatum, Aspergillus fumigatus, Ceratocystis ulmi, Pythium ultimum up to 89% with an IC50 value of 21.3-69.6 µL 50 mL-1 and caused leakage of soluble proteins and other intracellular molecules. Citrusy sweet odor volatiles of TML9 cultured in wheat-husk minimised the infections of Penicillium digitatum (green mold), in VOC-exposed sweet oranges (Citrus sinensis). Volatile and non-volatile antifungal metabolites of these two T. majus endophytes hold agricultural and pharmaceutical interests. Metabolites of TML3 have strong anti-Candida activity and require further assessment for therapeutic applications. Also, volatile metabolites of TML9 can be further studied as a source of antifungals. The present investigational outcomes bio-prospects the efficacy of fungal endophytes of Garden Nasturtium.


Subject(s)
Antifungal Agents , Endophytes , Volatile Organic Compounds , Volatile Organic Compounds/pharmacology , Volatile Organic Compounds/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Endophytes/metabolism , Endophytes/chemistry , Microbial Sensitivity Tests , Colletotrichum/drug effects , Fungi/drug effects , Alternaria/drug effects , Rhizoctonia/drug effects , Humans , Candida/drug effects
3.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2722-2727, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812172

ABSTRACT

This study investigated the chemical and biological activity of the secondary metabolites from an endophytic fungus Fusa-rium solani MBM-5 of Datura arborea. A total of six alkenoic acid compounds, including a new compound and five known ones, were isolated from the ethyl acetate extract of F. solani MBM-5 by using the chromatographic methods(open ODS column chromatography, silica gel column chromatography, Sephadex LH-20, and semi-preparative HPLC). The structures of the compounds were identified by using their physical and chemical data, spectroscopic methods(UV, IR, NMR, and HR-ESI-MS), and Mosher's reaction, which were fusaridioic acid E(1), fusaridioic acid C(2), fusaridioic acid A(3), L660282(4), hymeglusin(5), and hymeglnone(6). Compound 1 is new. MTT assay and Griss method were used to evaluate the growth inhibition of all the compounds against two tumor cells, as well as their influence and anti-inflammatory action on the release of NO from LPS-induced RAW264.7 cells. The results showed that compound 5 had strong growth inhibition activity against A549 and HepG2 cell lines, with IC_(50) values of 4.70 and 13.57 µmol·L~(-1), respectively. Compounds 1 and 6 significantly inhibited the release of NO from LPS-induced RAW264.7 cells, with IC_(50) values of 77.00 and 70.33 µmol·L~(-1), respectively.


Subject(s)
Endophytes , Fusarium , Secondary Metabolism , Fusarium/drug effects , Fusarium/chemistry , Mice , Humans , Animals , Endophytes/chemistry , Cell Line, Tumor , RAW 264.7 Cells , Molecular Structure , Nitric Oxide/metabolism , Cell Proliferation/drug effects
4.
J Agric Food Chem ; 72(19): 10970-10980, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38708787

ABSTRACT

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.


Subject(s)
Alkaloids , Aspergillus fumigatus , Endophytes , Alkaloids/pharmacology , Alkaloids/chemistry , Aspergillus fumigatus/drug effects , Endophytes/chemistry , Molecular Structure , Fusarium/drug effects , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Plant Leaves/microbiology , Plant Leaves/chemistry , Microbial Sensitivity Tests , China , Plant Diseases/microbiology
5.
Sci Prog ; 107(2): 368504241253675, 2024.
Article in English | MEDLINE | ID: mdl-38807531

ABSTRACT

Camptothecin (CPT) is an important alkaloid used for anticancer treatment. It is mainly produced by two endangered and overharvested Camptotheca acuminata and Nothapodytes nimmoniana plants. Endophytic fungi are promising alternative sources for CPT production. In the present study, fungi residing within explants of Ixora chinensis were isolated and their CPT-producing capability of their endophytes was verified via thin-layer chromatography, high-performance liquid chromatography, liquid chromatography/high resolution mass spectrometry, and nuclear magnetic resonance analyses and compared with standards. In addition, MTT and sulforhodamine B assays were selected to test the anticancer effect. The endophytic fungi collection of 62 isolates were assigned to 11 genera, with four common genera (Diaporthe, Phyllosticta, Colletotrichum, and Phomopsis) and seven less common genera (Penicillium, Botryosphaeria, Fusarium, Pestalotiopsis, Aspergillus, and Didymella). Moreover, the anticancer activity of extracts was assessed against human lung carcinoma (A549). Among eight potential extracts, only Penicillium sp. I3R2 was found to be a source of CPT, while the remaining seven extracts have not been discovered potential secondary compounds. Thus, other prominent endophytic fungi might be potential candidates of phytochemicals with anticancer properties.


Subject(s)
Antineoplastic Agents , Camptothecin , Endophytes , Fungi , Humans , Camptothecin/pharmacology , Camptothecin/chemistry , Camptothecin/biosynthesis , Endophytes/metabolism , Endophytes/isolation & purification , Endophytes/chemistry , Fungi/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , A549 Cells , Cell Line, Tumor
6.
Mar Drugs ; 22(4)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38667775

ABSTRACT

The genus Bruguiera, a member of the Rhizophoraceae family, is predominantly found in coastal areas as a mangrove plant, boasting a rich and diverse community of endophytes. This review systematically compiled approximately 496 compounds derived from both the Bruguiera genus and its associated endophytes, including 152 terpenoids, 17 steroids, 16 sulfides, 44 alkaloids and peptides, 66 quinones, 68 polyketides, 19 flavonoids, 38 phenylpropanoids, 54 aromatic compounds, and 22 other compounds. Among these, 201 compounds exhibited a spectrum of activities, including cytotoxicity, antimicrobial, antioxidant, anti-inflammatory, antiviral, antidiabetic, insecticidal and mosquito repellent, and enzyme inhibitory properties, etc. These findings provided promising lead compounds for drug discovery. Certain similar or identical compounds were found to be simultaneously present in both Bruguiera plants and their endophytes, and the phenomenon of their interaction relationship was discussed.


Subject(s)
Endophytes , Rhizophoraceae , Endophytes/chemistry , Humans , Rhizophoraceae/microbiology , Animals
7.
Fitoterapia ; 175: 105941, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38575089

ABSTRACT

Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.


Subject(s)
Antineoplastic Agents , Molecular Docking Simulation , Oxazolidinones , Humans , Cell Line, Tumor , Molecular Structure , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistry , Oxazolidinones/pharmacology , Oxazolidinones/isolation & purification , Endophytes/chemistry , China , Hypocreales/chemistry
8.
Fitoterapia ; 175: 105943, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38575090

ABSTRACT

Three new sorbicillinoids sorbicatechols E-G (1-3), along with seven known compounds 4-10, were obtained from the ethanol extract of Penicillium sp. HS-11, a fungal endophyte of the medicinal plant Huperzia serrata. The structures of 1-3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the ECD spectra. Sorbicatechol G (3) represented the first hybrid sorbicillinoid bearing a tetralone skeleton. In the in-vitro bioassay, trichodimerol (5) exhibited moderate inhibitory activity against the Escherichia coli ß-glucuronidase (EcGUS) with an IC50 value of 92.0 ± 9.4 µM.


Subject(s)
Endophytes , Huperzia , Penicillium , Penicillium/chemistry , Endophytes/chemistry , Molecular Structure , Huperzia/microbiology , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Secondary Metabolism , China
9.
Fitoterapia ; 175: 105931, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608733

ABSTRACT

Pararorine A, a new isoindolinone alkaloid was isolated from Paramyrothecium roridum, an endophytic fungus from the medicinal plant Gynochthodes officinalis (F.C. How) Razafim. & B. Bremer. The structure of this compound was elucidated by extensive spectroscopic (UV, IR, MS, and NMR) analyses. In addition, the antitumor activity of pararorine A was evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that pararorine A exhibited potent antitumor activities with the IC50 values ranging from 1.69 to 8.95 µM. Moreover, the tumor cell inhibitory activity of pararorine A was evidenced by promoting cytochrome C release and cell cycle arrest as well as the induction of apoptosis by the up-regulation of the protein expressions of JNK and Bax through PARP-cleavage and caspase 3-cleavage.


Subject(s)
Apoptosis , Humans , Molecular Structure , Cell Line, Tumor , Apoptosis/drug effects , Endophytes/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , Alkaloids/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistry , Cell Cycle Checkpoints/drug effects , China
10.
Fitoterapia ; 175: 105952, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38614405

ABSTRACT

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.


Subject(s)
Endophytes , Xanthones , Xanthones/isolation & purification , Xanthones/pharmacology , Xanthones/chemistry , Molecular Structure , Humans , Endophytes/chemistry , Cell Line, Tumor , Pogostemon/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistry , China
11.
Fitoterapia ; 175: 105983, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679297

ABSTRACT

Phytochemical investigation on the extract of endophytic fungus Tolypocladium sp. SHJJ1 resulted in the identification of a pair of previously undescribed pyridoxatin atropisomers [1 (M/P)] and three new indole diterpenoids (3-5), together with a pair of known pyridoxatin atropisomers [2 (M/P)] and ten known indole diterpenoids (6-15). Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Among the undescribed natural products, [1 (M/P)] that two rapidly interconverting atropisomers are the third example to report in the pyridoxatin atropisomers. Except for compounds 1 (M/P) and 2 (M/P), all other compounds were tested for their cytotoxicity using HepG2, A549, and MCF-7 human cell lines. Compound 9 displayed moderate cytotoxicity against the HepG2, A549, and MCF-7 cell lines with IC50 values of 32.39 ± 1.48 µM, 26.06 ± 1.14 µM, and 31.44 ± 1.94 µM, respectively, which was similar to the positive drug cisplatin (with IC50 values of 32.55 ± 1.76 µM, 18.40 ± 1.43 µM, and 27.31 ± 1.22 µM, respectively).


Subject(s)
Diterpenes , Indoles , Humans , Diterpenes/pharmacology , Diterpenes/isolation & purification , Diterpenes/chemistry , Molecular Structure , Indoles/isolation & purification , Indoles/pharmacology , Indoles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistry , Endophytes/chemistry , China , Hypocreales/chemistry , Cell Line, Tumor , Ascomycota/chemistry
12.
Arch Microbiol ; 206(5): 229, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647675

ABSTRACT

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.


Subject(s)
Resveratrol , Stilbenes , Stilbenes/chemistry , Stilbenes/pharmacology , Humans , Resveratrol/pharmacology , Resveratrol/chemistry , Fungi/drug effects , Endophytes/chemistry , Endophytes/metabolism , Endophytes/isolation & purification , Antioxidants/chemistry , Antioxidants/pharmacology , Medicine, Traditional , Plants/chemistry
13.
Phytochemistry ; 222: 114103, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636686

ABSTRACT

Eight new cytochalasans rosellichalasins A-H (1-8), as well as two new shunt metabolites rosellinins A (9) and B (10) before intramolecular Diels-Alder cycloaddition reaction in cytochalasan biosynthesis, along with nine known cytochalsans (11-19) were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata. Their structures were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra and quantum chemical ECD calculations. The cytotoxic activities of these compounds were evaluated against four human cancer cell lines including HCT116, MDA-MB-231, BGC823, and PANC-1 with IC50 values ranging from 0.5 to 58.2 µM.


Subject(s)
Antineoplastic Agents , Cytochalasins , Drug Screening Assays, Antitumor , Xylariales , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cytochalasins/chemistry , Cytochalasins/pharmacology , Cytochalasins/isolation & purification , Dose-Response Relationship, Drug , Endophytes/chemistry , Molecular Structure , Structure-Activity Relationship , Xylariales/chemistry , Xylariales/classification
14.
Front Biosci (Landmark Ed) ; 29(3): 111, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38538270

ABSTRACT

BACKGROUND: Bacterial endophytic communities associated with medicinal plants synthesize a plethora of bioactive compounds with biological activities. Their easy isolation and growth procedures make bacterial endophytes an untapped source of novel drugs, which might help to face the problem of antimicrobial resistance. This study investigates the antagonistic potential of endophytic bacteria isolated from different compartments of the medicinal plant O. heracleoticum against human opportunistic pathogens. METHODS: A panel of endophytes was employed in cross-streaking tests against multidrug-resistant human pathogens, followed by high-resolution chemical profiling using headspace-gas chromatography/mass spectrometry. RESULTS: Endophytic bacteria exhibited the ability to antagonize the growth of opportunistic pathogens belonging to the Burkholderia cepacia complex (Bcc). The different inhibition patterns observed were related to their taxonomic attribution at the genus level; most active strains belong to the Gram-positive genera Bacillus, Arthrobacter, and Pseudarthrobacter. Bcc strains of clinical origin were more sensitive than environmental strains. Cross-streaking tests against other 36 human multidrug-resistant pathogens revealed the highest antimicrobial activity towards the Coagulase-negative staphylococci and Klebsiella pneumoniae strains. Interestingly, strains of human origin were the most inhibited, in both groups. Concerning the production of volatile organic compounds (VOCs), the strain Arthrobacter sp. OHL24 was the best producer of such compounds, while two Priestia strains were good ketones producers and so could be considered for further biotechnological applications. CONCLUSIONS: Overall, this study highlights the diverse antagonistic activities of O. heracleoticum-associated endophytes against both Bcc and multidrug-resistant (MDR) human pathogens. These findings hold important implications for investigating bacterial endophytes of medicinal plants as new sources of antimicrobial compounds.


Subject(s)
Origanum , Plants, Medicinal , Humans , Endophytes/chemistry , Bacteria , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
15.
Fitoterapia ; 175: 105914, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38508500

ABSTRACT

The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied the OSMAC-approach to the endophytic fungus Trichocladium sp. by supplementation of the cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic acid (3), colletolactone (4) and colletolic acid (5), together with five previously described ones (6-10). The structures were elucidated via comprehensive spectroscopic measurements, and the absolute configurations of compound 1 was elucidated by using TDDFT-ECD calculations. For formation of compounds 3-5, a pathway based on colletodiol biosynthesis is proposed. Compound 6 exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 0.78 µM as well as a strong cytotoxic effect against the human monocytic cell line THP1 with an IC50 of 0.7 µM. Compound 8 showed moderate antibacterial activity against Mycobacterium tuberculosis with a MIC of 25 µM and a weak cytotoxic effect against THP1 cells with an IC50 of 42 µM.


Subject(s)
Anti-Bacterial Agents , Endophytes , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Molecular Structure , Methicillin-Resistant Staphylococcus aureus/drug effects , Mycobacterium tuberculosis/drug effects , Endophytes/chemistry , Hypocreales/chemistry , THP-1 Cells , China
16.
Z Naturforsch C J Biosci ; 79(3-4): 89-92, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38421614

ABSTRACT

A novel isocoumarin was isolated from the mycelia of the dark septate endophytic fungus Phialocephala fortinii. The chemical structure was determined to be 8-hydroxy-6-methoxy-3,7-dimethyl-1H-2-benzopyran-1-one based on mass spectrometry, 1H-nuclear magnetic resonance (NMR), and 13C-NMR spectroscopic analyses, including 2D-NMR experiments. The isolated compound inhibited root growth of Arabidopsis thaliana, suggesting its potential as a plant growth regulator.


Subject(s)
Arabidopsis , Ascomycota , Isocoumarins , Plant Roots , Isocoumarins/chemistry , Isocoumarins/pharmacology , Isocoumarins/isolation & purification , Ascomycota/chemistry , Plant Roots/microbiology , Arabidopsis/microbiology , Magnetic Resonance Spectroscopy , Endophytes/chemistry , Mycelium/growth & development , Mycelium/chemistry , Mycelium/drug effects , Plant Growth Regulators/pharmacology , Plant Growth Regulators/chemistry , Molecular Structure
17.
Ann Bot ; 133(4): 509-520, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38320313

ABSTRACT

BACKGROUND AND AIMS: In the subfamily Poöideae (Poaceae), certain grass species possess anti-herbivore alkaloids synthesized by fungal endophytes that belong to the genus Epichloë (Clavicipitaceae). The protective role of these symbiotic endophytes can vary, depending on alkaloid concentrations within specific plant-endophyte associations and plant parts. METHODS: We conducted a literature review to identify articles containing alkaloid concentration data for various plant parts in six important pasture species, Lolium arundinaceum, Lolium perenne, Lolium pratense, Lolium multiflorum|Lolium rigidum and Festuca rubra, associated with their common endophytes. We considered the alkaloids lolines (1-aminopyrrolizidines), peramine (pyrrolopyrazines), ergovaline (ergot alkaloids) and lolitrem B (indole-diterpenes). While all these alkaloids have shown bioactivity against insect herbivores, ergovaline and lolitrem B are harmful for mammals. KEY RESULTS: Loline alkaloid levels were higher in the perennial grasses L. pratense and L. arundinaceum compared to the annual species L. multiflorum and L. rigidum, and higher in reproductive tissues than in vegetative structures. This is probably due to the greater biomass accumulation in perennial species that can result in higher endophyte mycelial biomass. Peramine concentrations were higher in L. perenne than in L. arundinaceum and not affected by plant part. This can be attributed to the high within-plant mobility of peramine. Ergovaline and lolitrem B, both hydrophobic compounds, were associated with plant parts where fungal mycelium is usually present, and their concentrations were higher in plant reproductive tissues. Only loline alkaloid data were sufficient for below-ground tissue analyses and concentrations were lower than in above-ground parts. CONCLUSIONS: Our study provides a comprehensive synthesis of fungal alkaloid variation across host grasses and plant parts, essential for understanding the endophyte-conferred defence extent. The patterns can be understood by considering endophyte growth within the plant and alkaloid mobility. Our study identifies research gaps, including the limited documentation of alkaloid presence in roots and the need to investigate the influence of different environmental conditions.


Subject(s)
Alkaloids , Endophytes , Epichloe , Festuca , Lolium , Polyamines , Alkaloids/metabolism , Alkaloids/analysis , Endophytes/chemistry , Endophytes/physiology , Epichloe/chemistry , Epichloe/physiology , Ergotamines/metabolism , Festuca/microbiology , Festuca/physiology , Herbivory , Heterocyclic Compounds, 2-Ring , Indole Alkaloids/metabolism , Lolium/microbiology , Lolium/physiology , Mycotoxins , Plant Defense Against Herbivory , Poaceae/microbiology , Poaceae/metabolism , Symbiosis
18.
Pest Manag Sci ; 80(6): 2658-2667, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38284314

ABSTRACT

BACKGROUND: Phytopathogenic bacteria cause severe losses to crops every year. The management of crop bacterial diseases with chemical agents has been considered as the main strategy. In order to cope with the bactericide resistance made by the pathogens, new antibacterials need to be continuously developed. RESULTS: A chemical investigation from the endophytic fungus Rhexocercosporidium sp. Dzf14 has led to the isolation of 12 diphenyl ethers including two new ones named rhexocerin E (1) and rhexocercosporin G (2), along with two new depsides named rhexocerdepsides A (3) and B (4). The structures and absolute configurations of the new compounds were determined through comprehensive analysis of spectroscopic data and quantum chemical ECD calculations. Diphenyl ethers showed obviously antibacterial activity on Gram-positive bacteria. The structure-activity relationship of diphenyl ethers revealed that prenylation was critical to the antibacterial activity. Among them, rhexocercosporin D (12) possessed the strongest activity against Clavibacter michiganensis and Bacillus subtilis, and was selected for further mechanistic studies. It was found that rhexocercosporin D displayed bactericidal activity by affecting homeostasis of cell membranes. In addition to its rapid bactericidal effects on Gram-positive bacteria, rhexocercosporin D could restore the susceptibility against Gram-negative Agrobacterium tumefaciens by synergistic action with colistin. CONCLUSION: Twelve diphenyl ethers and two depsides were isolated from endophytic fungus Rhexocercosporidium sp. Dzf14. Isopentenyl was critical for diphenyl ethers against Gram-positive bacteria. Rhexocercosporin D could affect homeostasis of bacterial cell membrane to exert rapid bactericidal activity. These findings highlight the antibacterial potential of the diphenyl ethers in crop bacterial disease management. © 2024 Society of Chemical Industry.


Subject(s)
Anti-Bacterial Agents , Cell Membrane , Homeostasis , Phenyl Ethers , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell Membrane/drug effects , Phenyl Ethers/pharmacology , Phenyl Ethers/chemistry , Endophytes/chemistry , Structure-Activity Relationship , Gram-Positive Bacteria/drug effects , Molecular Structure
19.
Nat Prod Res ; 38(4): 696-700, 2024.
Article in English | MEDLINE | ID: mdl-36896764

ABSTRACT

Fungal endophytes are valued for biosynthesizing chemically diverse metabolic cascade with interesting biological activities. In the current investigation, two compounds were isolated from Penicillium polonicum, an endophyte of Zingiber officinale. The active moieties, glaucanic acid (1) and dihydrocompactin acid (2) were isolated from the ethyl acetate extract of P. polonicum and characterized by NMR and mass spectroscopy. Further, bioactive potential of the isolated compounds was evaluated by antimicrobial, antioxidant and cytotoxicity assays. Compounds 1 and 2 displayed antifungal activity against phytopathogen Colletotrichum gloeosporioides with more than 50% reduction in its growth. Both the compounds exhibited antioxidant activity against free radicals (DPPH and ABTS) and cytotoxicity activity against cancer cell lines respectively. The compounds, glaucanic acid and dihydrocompactin acid are being reported for the first time from an endophytic fungus. This is the first report on the biological activities of Dihydrocompactin acid produced by endophytic fungal strain.


Subject(s)
Lovastatin/analogs & derivatives , Penicillium , Zingiber officinale , Penicillium/chemistry , Fungi , Antioxidants/pharmacology , Antioxidants/metabolism , Endophytes/chemistry
20.
BMC Microbiol ; 23(1): 343, 2023 11 16.
Article in English | MEDLINE | ID: mdl-37974074

ABSTRACT

Endophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1-26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.


Subject(s)
Anti-Infective Agents , Nigella sativa , Humans , Endophytes/chemistry , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Seeds , Fungi
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