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Indole alkaloids are privileged secondary metabolites, and their production may be achieved by the microbial biotransformation of tryptophan analogues. By feeding 1-methyl-L-tryptophan (1-MT) into the culture of endophytic Nigrospora chinensis GGY-3, six novel ( 1 - 6 ) and seven known indole alkaloids ( 7 - 13 ) were generated. Their structures were elucidated by means of NMR spectroscopy, experimental electronic circular dichroism (ECD) spectra, and X-ray crystallography analysis. A Friedel-Crafts reaction was proposed as the key reaction responsible for the formation of the new compounds. Racemates 4 and 6 were separated into isomers by chiral HPLC, with their absolute configurations determined by X-ray and ECD calculation. Compounds 3 , 4 , and 8 display good herbicidal activity against dicotyledon weed Eclipta prostrata , of which 4 and 8 exhibited 88.50% and 100% inhibition rates on the radicle at 200 μg/mL, respectively, a similar effect compared to the positive control penoxsulam.

We recently discovered that sphaeropsidin A (SphA), a fungal metabolite from Diplodia cupressi, overcomes apoptosis resistance in cancer cells by inducing cellular shrinkage by impairing regulatory volume increase. Previously, we prepared a pyrene-conjugated derivative of SphA by a cross-metathesis reaction involving the phytotoxin's C15,C16-alkene. This derivative's evaluation in a cancer cell panel revealed a significant increase in potency, with the IC 50 values 5-10× lower than those displayed by the original natural product. Herein, we describe the preparation and anticancer evaluation of fifteen novel C15,C16-alkene cross-metathesis analogues in which the pyrene moiety was replaced with other aromatic or non-aromatic hydrophobic groups. The idea for this replacement was to prepare a family of compounds that would not be predicted to be mutagenic compared with the original pyrene analogue. We predict several of our new compounds to be non-mutagenic, while retaining the high potency of the original pyrene-containing analogues. Examples of these potential lead compounds included those containing pentamethylphenyl and triphenylethylene pendant groups. As an additional feature of the current investigation, we prepared several deuterated pyrene-containing compounds to overcome intellectual property issues associated with non-patentability of the original pyrene derivative., (© 2024 Wiley-VCH GmbH.)

The Dothideomycete fungal pathogen Pyrenophora tritici-repentis (Ptr) is the causal agent of the tan spot disease of wheat. The proteinaceous necrotrophic effectors ToxA and ToxB are well characterized. A nonproteinaceous effector called ToxC has also been partially characterized. Ptr produces a number of other small molecular weight compounds, but these remain poorly characterized. In this study, two novel compounds, designated ToxE1 and ToxE2, capable of inducing chlorotic symptoms on wheat leaves in a cultivar-specific manner, were purified from Ptr liquid cultures. There is no evidence that these compounds correspond to ToxC. Most isolates produced ToxE1, ToxE2, or both, and both compounds were detected in infected wheat leaves. The structures of both analogues were elucidated by NMR spectroscopy and comprise a phthalide core structure with an amide moiety. We postulate that these compounds have a general phytotoxic effect and may have an ancillary role in disease development.

Honey truffle sweetener (HTS), a 121 amino acid protein is identified as a high-intensity sweetener found naturally occurring in the Hungarian Sweet Truffle Mattirolomyces terfezioides , an edible mushroom used in regional diets. The protein is intensely sweet, but the truffle is difficult to cultivate; therefore, the protein was systematically characterized, and the gene coding for the protein was expressed in a commonly used host yeast Komagataella phaffii . The heterologously expressed protein maintained the structural characteristics and sweet taste of the truffle. Preliminary safety evaluations for use as a food ingredient were performed on the protein including digestibility and in silico approaches for predicting the allergenicity and toxicity of the protein. HTS is predicted to be nonallergenic, nontoxic, and readily digestible. This protein is readily produced by precision fermentation of the host yeast, making it a potential replacement for both added sugars and small molecule high-intensity sweeteners in food.

Background: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans., Results: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively., Conclusion: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture., (© 2024. The Author(s).)

The black morel (Morchella sextelata) is a valuable edible and medicinal mushroom appreciated worldwide. Here, lipidomic profiles and lipid dynamic changes during the growth of M. sexletata were analyzed using ultra-performance liquid chromatography coupled with mass spectrometry. 203 lipid molecules, including four categories and fourteen subclasses, were identified in mature fruiting bodies, with triacylglycerol being the most abundant (37.00 %). Fatty acid composition analysis revealed that linoleic acid was the major fatty acid among the free fatty acids, glycerolipids and glycerophospholipids. The relative concentration of lipids in M. sextelata changed significantly during its growth, from which 12 and 29 differential lipid molecules were screened out, respectively. Pathway analysis based on these differential lipids showed that glycerophospholipid metabolism was the major pathway involved in the growth of M. sextelata. Our study provides a comprehensive understanding of the lipids in M. sextelata and will facilitate the development and utilization of M. sextelata., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

An undescribed α-pyrone diaporpyrone E ( 1 ), and three known nucleotides, 5'-O-acetyl uridine ( 2 ), 5'-O-acetyl thymidine ( 3 ), and adenine ( 4 ), were identified from Diaporthe sp. CB10100, an endophytic fungus isolated from the medicinal plant Sinomenium acutum . The structure of 1 was determined by extensive analysis of its HRMS, 1D and 2D NMR spectroscopic data, as well as electronic circular dichroism calculations and comparison. The in vitro cytotoxic and antibacterial assays of 1 revealed that it has a 30.2% inhibitory effect on HepG2 cells at 50 μM, while no antibacterial activities against Staphylococcus aureus and Klebsiella pneumoniae at 64 μg/mL.

Hypoxylon vinosopulvinatum DYR-1-7 is a endophytic fungus isolated from the Cinnamomum cassia Presl and has an inhibitory effect on Lasiodiplodia pseudotheobromae . Three new furanones, hypoxylonone A-C ( 1 - 3 ), as well as three known compounds ( 4 - 6 ), were isolated from an EtOAc extract of H. vinosopulvinatum DYR-1-7. The structures were determined by spectroscopic data analysis using UV, IR, 1D-, 2D-NMR and HR-ESI-MS. The absolute configurations of 1 - 3 were elucidated by electronic circular dichroism (ECD) analyses. In the antifungal bioassay, Hypoxylonone B and C exhibited strong inhibitory effects on L. pseudotheobromae with IC 50 value at the concentration of 1.01 and 2.40 μg/mL, respectively. Compound 6 showed medium antifungal activity with IC 50 value at the concentration of 10.67 μg/mL on Fusarium oxysporum . Compounds 3 and 4 displayed medium antifungul effects on Candida albicans .

Understanding the stereoselective bioactivity of chiral pesticides is crucial for accurately evaluating their effectiveness and optimizing their use. Isopyrazam, a widely used chiral SDHI fungicide, has been studied for its antifungal activity only at the racemic level. Therefore, to clarify the highly bioactive isomers, the stereoselective bioactivity of isopyrazam isomers against four typical phytopathogens was studied for the first time. The bioactivity ranking of the isomers was trans- 1 S ,4 R ,9 R - (+)-isopyrazam > cis -1 R ,4 S ,9 R -(+)-isopyrazam > trans -1 R ,4 S ,9 S -(-)-isopyrazam > cis- 1 S ,4 R ,9 S -(-)-isopyrazam. SDH activity was assessed by molecular docking simulation and actual detection to confirm the reasons for stereoselective bioactivity. The results suggest that the stereoselective bioactivity of isopyrazam is largely dependent on the differential binding ability of each isomer to the SDH ubiquitin-binding site, located within a cavity formed by the iron-sulfur subunit, the cytochrome b560 subunit, and the cytochrome b small subunit. Moreover, to reveal the molecular mechanism of isopyrazam stereoselectively affecting mycelial growth, the contents of succinic acid, fumaric acid, and ATP were measured. Furthermore, by measuring exospore polysaccharides and oxalic acid content, it was determined that 1 S ,4 R ,9 R -(+)- and 1 R ,4 S ,9 R -(+)-isopyrazam more strongly inhibited the ability of Sclerotinia sclerotiorum to infect plants. The findings provided essential data for the development of high-efficiency isopyrazam fungicides and offered a methodological reference for analyzing the enantioselective activity mechanism of SDHI fungicides.

Hydrophobins (HFBs) and cerato-platanins (CPs) are surface-active extracellular proteins produced by filamentous fungi. This study identified two HFB genes (pshyd1 and pshyd2) and one CP gene (pscp) in the marine fungus Paradendryphiella salina. The proteins PsCP, PsHYD2, and PsHYD1 had molecular weights of 12.70, 6.62, and 5.98 kDa, respectively, with isoelectric points below 7. PsHYD1 and PsHYD2 showed hydrophobicity (GRAVY score 0.462), while PsCP was hydrophilic (GRAVY score - 0.202). Stability indices indicated in-solution stability. Mass spectrometry identified 2,922 proteins, including CP but not HFB proteins. qPCR revealed differential gene expression influenced by developmental stage and substrate, with pshyd1 consistently expressed. These findings suggest P. salina's adaptation to marine ecosystems with fewer hydrophobin genes than other fungi but capable of producing surface-active proteins from seaweed carbohydrates. These proteins have potential applications in medical biocoatings, food industry foam stabilizers, and environmental bioremediation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new ( 1 and 2 ) and four known ( 3 - 6 ) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis . Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster ( alt ) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH 3 to a carboxyl group to produce 4 from 3 . Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1 , 2 , 5 , and 6 from 4 . Alternapyrone G ( 1 ) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

Postharvest harmful pathogenic infestation leads to rapid decay in longan fruit. Compared with P. longanae-infected longans, AEOW alleviated fruit disease severity and diminished the O 2 -. production rate and MDA content. It also increased APX, CAT, and SOD activities, delayed the decrease in the levels of GSH and AsA, as well as the reducing power and DPPH radical scavenging ability, which resulted in a decline in membrane lipid peroxidation in P. longanae-infected longans. Additionally, AEOW reduced LOX, lipase, PI-PLC, PC-PLC, and PLD activities, maintained higher levels of PC, PI, IUFA, USFAs, and U/S, while reducing levels of PA, DAG, SFAs, and CMP. These effects alleviated membrane lipid degradation and peroxidation in P. longanae-infected longans. Consequently, AEOW effectively maintained membrane integrity via improving antioxidant capacity and suppressing membrane lipid peroxidation. This comprehensive coordination of ROS and membrane lipid metabolisms improved fruit resistance and delayed disease development in longans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recently, the demand for new antifungal drugs has increased due to the presence of antimicrobial resistant bacteria and their side effects. Occidiofungins (Ocfs) are cyclic lipo-octapeptides that possess unusual amino acids and potent antifungal activities. However, the chemical structure of the 2,4-diamino butyric acid (Dab) residue in the backbone of Ocfs has not been clarified thus far. Therefore, we conducted a structural analysis of the tripeptides around the Dab residue in Ocfs using 1 H-NMR spectroscopy. We determined that the D-Dab residue in the peptide backbone of Ocfs has an α-amino linkage. Additionally, we found that Ocf A (5) and Bk-1119 have the same chemical structure. Moreover, the analogue possessing D-αDab (13) showed potent antifungal activity against A. oryzae.

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC 50 = 0.170 μg/mL), outperforming carbendazim (EC 50 = 0.360 μg/mL) and boscalid (EC 50 = 1.36 μg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali , Botrytis cinerea , and Alternaria alternata with EC 50 values of 0.590, 0.870, and 1.71 μg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti- R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC 50 = 8.42 μM), surpassing that of the SDH fungicide boscalid (IC 50 = 15.6 μM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.

The discovery of readily available and easily modifiable new models is a crucial and practical solution for agrochemical innovation. Antifungal function-oriented fusion of triazole with the prevalidated lead ( R )- LE001 affords a novel framework with a broad and enhanced antifungal spectrum. Characterized by the easy accessibility and adjustability of [1,2,4]triazolo[4,3- a ]pyridine, modular fine-tuning provided a set of unprecedented leads (e.g., Z23 , Z25 , Z26 , etc.) with superior antifungal potentials than the positive control boscalid. Candidate Z23 exhibited a more promising antifungal activity against Sclerotinia sclerotiorum , Botrytis cinerea , and Phytophthora capsici with EC 50 values of 0.7, 0.6, and 0.5 μM, respectively. This candidate could effectively control boscalid-resistant B. cinerea strains and also exhibit good vivo efficacy in controlling gray mold. Noteworthily, both the SDH-inhibition and the efficiency against Oomycete P. capsici are quite distinct from that of the positive control boscalid. A molecular docking simulation also differentiates Z23 from boscalid. These findings highlight the potential of [1,2,4]triazolo[4,3- a ]pyridine amide as a novel antifungal model.

A new 14-membered resorcylic acid lactone (RAL 14 ), chaetolactone A ( 1 ), along with three known ones ( 2 - 4 ), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR), 13 C NMR chemical shifts calculations coupled with the DP4 + probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED 50 s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A new heptaketide named oryzanigral ( 1 ) was isolated from the fermentation extract of the endophytic fungus Nigrospora oryzae isolated from the leaves of Coccinia grandis , along with five known compounds, ( R )-mellein, (R )- O -methylmellein, (3 R ,4 R )-4-hydroxymellein, (3 R ,4 S )-4-hydroxymellein and abscisic acid. The structure of oryzanigral was elucidated by spectroscopic analyses including 2D-NMR. A plausible biosynthetic pathway involving Diels-Alder reaction was proposed for compound 1 and related polyketides previously reported. In addition, structure revision of the double bond geometry for coicenal A was described.

Dothiorella species are fungal plant pathogens associated with Botryosphaeria dieback of grapevine. Symptoms caused by these fungi on grapevines suggest possible implication of phytotoxic metabolites in the infection mechanisms. However, few studies were conducted to investigate the secondary metabolism of these fungi. In this study, 6-methylpyridione analogues were isolated and identified for the first time in liquid cultures of Dothiorella sarmentorum isolated from symptomatic grapevine in Algeria.

Diaporthpyran A ( 1 ), diaporthester E ( 2 ) and diaporthester F ( 3 ), three new compounds along with four known compounds ( 4 - 7 ) were isolated from the crude extract of Diaporthe biguttusis T-24, an endophytic fungus isolated from Ligularia fischeri . The planar structures of compounds 1 - 3 including the relative and absolute configurations were elucidated on the basis of HRMS, NMR, J -based coupling constant analysis, CD, and calculated ECD analysis. In addition, compounds 1 and 3 were evaluated for their cytotoxic activities against four human cancer cell lines.

Melanins are heterogenous biopolymers produced by many macro and microorganisms. They enhance the ecological fitness of the producer organisms by improving their virulence and protecting them from radiation, osmotic and heat stresses. Fungi synthesise either DOPA or DHN melanin and deposit them on their cell walls. Some fungal isolates produce water soluble melanin (pyomelanin) which is excerted out of the hyphae into the surrounding environment. Pyomelanin, a polymer of homogentisate, exhibits antimicrobial, UV screening, antioxidative, and anti-inflammatory activities and recent studies also show that pyomelanin could find use in space travel as radiation shield. However, scant literature is available on fungi with ability to produce pyomelanin. We report for the first time that Amorosia littoralis occurs as a root endophyte in mangrove species including Avicennia marina, Bruguiera cylindrica and Bruguiera gymnorhiza and produces pyomelanin. Considering the various technological uses of pyomelanin, this study underscores the need to explore fungi of different habitats to identify hyperproducers and to obtain chemically diverse pyomelanin., (Copyright © 2024 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Citrus black spot (CBS) is a fungal disease caused by Phyllosticta citricarpa Kiely, (McAlpine Van der Aa), with most cultivars being susceptible to infection. Currently, disease control is based on the application of protective fungicides, which is restricted due to resistance, health and environmental concerns. Although using natural products for disease management is gaining momentum, more advances are required. This study obtained the metabolic profiles of the essential oil and cuticular waxes of two citrus cultivars with a varying susceptibility to CBS infection using gas chromatography-mass spectrometry. A multivariate data analysis identified possible biomarker compounds that contributed to the difference in susceptibility between the two cultivars. Several identified biomarkers were tested in vitro for their antifungal properties against P. citricarpa . Two biomarkers, propanoic acid and linalool, were able to completely inhibit pathogen growth at 750 mg/L and 2000 mg/L, respectively.

Cavoxin ( 1 ) was isolated as the main phytotoxin produced by Phoma cava Schulzer, a toxigenic fungus isolated from Castanea spp. Its structure was determined by 1D NMR and MS in 1985 along with that of the corresponding chroman-4-one cavoxone ( 2 ), an artifact formed by acid treatment of 1 . Since that time cavoxin was shown to be phytotoxic, antifungal, antifeedant, herbicidal, and antirust with potential application in agriculture and medicine. During a study aimed at improving cavoxin's production by P. cava , single crystals for X-ray diffractometric analysis were obtained. The X-ray crystallography characterization confirmed only in part the structure proposed for cavoxin ( 1 ), revealing a different substitution pattern on the aromatic ring, as depicted in the revised structure 3 .

Thin layer chromatography-direct bioautography (TLC-DB) is a well-established bioassay used to separate and identify natural products (NPs) that are antagonistic against a target pathogen. It is a rapid, inexpensive, and simple option for the bioassay-guided isolation and identification of NPs that hinges on separation by TLC coupled with the direct application of a target pathogen to examine bioactivity. It is typically used for the analysis of bioactive plant extracts, detecting inhibitory activity against bacteria, fungi, and enzymes. That being said, it has great potential in bacterial NP discovery, particularly for evaluating bacterial NPs against pertinent agricultural pathogens, which is valuable for discovering and developing novel biopesticides for the agriculture industry. Furthermore, it is a tunable protocol that could be applied to other target pathogens or sources of NPs in research programs concerning the discovery and identification of bioactive compounds. Herein, we describe a model system for discovering and identifying biopesticide NPs using TLC-DB with Bacillus spp. and the agricultural pathogen Sclerotinia sclerotiorum.

In our screening program for natural products that are effective in controlling plant diseases, we found that the culture filtrate of Paraconiothyrium sporulosum SFC20160907-M11 effectively suppressed the development of tomato late blight disease caused by Phytophthora infestans . Using a bioassay-guided fractionation of antioomycete activity, 12 active compounds ( 1 - 12 ) were obtained from an ethyl acetate extract of the culture filtrate. Chemical structures of five new compounds 1 - 5 were determined by the extensive analyses of nuclear magnetic resonance (NMR), high resolution mass spectrometry (HRMS), and circular dichroism (CD) data. Interestingly, mycosporulonol ( 1 ) and botrallin ( 8 ) completely inhibited the growth of P. infestans at concentrations of 8 and 16 μg/mL, respectively. Furthermore, the spray treatment of 1 and 8 (500 μg/mL) successfully protected tomato seedlings against P. infestans with disease control values of 92%. Taken together, these results suggest that the culture filtrates of P. sporulosum SFC20160907-M11 and their bioactive metabolites can be used as new antioomycete agents for Phytophthora late blight control.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1 H -benzo[ d ]imidazole ( A 25 ) exhibited optimal antifungal activity against Sclerotinia sclerotiorum ( S. s. ), affording an excellent half-maximal effective concentration (EC 50 ) of 0.158 μg/mL, which was higher than that of the reference agent carbendazim (EC 50 = 0.594 μg/mL). Pot experiments revealed that compound A 25 (200 μg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A 25 and β-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A 25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

A study targeting novel antifungal metabolites identified potent in vitro antifungal activity against key plant pathogens in acetone extracts of Streptomyces sp. strain CA-296093. Feature-based molecular networking revealed the presence in this extract of antimycin-related compounds, leading to the isolation of four new compounds: escuzarmycins A-D ( 1 - 4 ). Extensive structural elucidation, employing 1D and 2D NMR, high-resolution mass spectrometry, Marfey's analysis, and NOESY correlations, confirmed their structures. The bioactivity of these compounds was tested against six fungal phytopathogens, and compounds 3 and 4 demonstrated strong efficacy, particularly against Zymoseptoria tritici , with compound 3 exhibiting the highest potency (EC 50 : 11 nM). Both compounds also displayed significant antifungal activity against Botrytis cinerea and Colletotrichum acutatum , with compound 4 proving to be the most potent. Despite moderate cytotoxicity against the human cancer cell line HepG2, compounds 3 and 4 emerge as promising fungicides for combating Septoria tritici blotch, anthracnose, and gray mold.

Neocosmospora solani causes Fusarium wilt disease and root rot, which are serious problems worldwide. To determine the growth inhibition of Neocosmospora solani by Trichoderma hamatum volatile organic compounds (VOCs), the major chemical components of Trichoderma hamatum VOCs and the differences in their contents at different times were analysed, and the activity of these components was evaluated. The antifungal activity of Trichoderma hamatum was measured by a screening test, as Trichoderma hamatum exhibited strong antagonism against Neocosmospora solani in vitro. The double plate technique was used to verify the activity of Trichoderma hamatum VOCs, and the inhibition rate was 63.77%. Neocosmospora solani mycelia were uneven and expanded, the contents of the cells leaked, and the mycelia shrank and presented a diaphragm in the hyphae upon Trichoderma hamatum VOCs treatment. Trichoderma hamatum VOCs and their contents at different times were analysed by using gas chromatography-mass spectrometry. 6-Pentyl-2H-pyran-2-one clearly presented in greater amounts than the other components on day 3, 4, 5, and 6. VOCs from Trichoderma hamatum exhibited evident effects on the percentage of healthy fruit after day 3. Moreover, Trichoderma hamatum can improve the biological control of diseases caused by soilborne pathogens, and can be applied in biocontrol fields., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

The synergism of host Paris polyphylla medium, the monoculture, and the coculture led to seventeen new metabolites, including eight sesquiterpenes, 1-7 having uncommon structural motifs compared to similar caryophyllene derivatives, 8 with an unprecedented bicyclic framework, and three xyloketals (13-15) with unprecedented frameworks from Nigrospora lacticolonia; one polyketide, 17 with novel bicyclo [2.2.2] undecane skeleton, and five polyketide-terpenoid hybrids, 20 (one novel sulfated), 21-24 from Penicillium rubens. The structures were determined mainly by the NMR, HRESIMS, ECD calculation, and single-crystal X-ray diffraction. Nine cryptic compounds (2-4, 5, 12-15, 17) were produced by the inductions of host medium and the coculture. The compounds 13 from N. lacticolonia, 24-26, 28, 29, and 31 from P. rubens indicated significant antiphytopathogenic activities against N. lacticolonia with MICs at 2-4 μg/mL. Moreover, compounds 22-26, 28, 29, and 31 from P. rubens showed antifungal activities against P. rubens with MICs at 2-4 μg/mL. The synergistic effects of host medium and the coculture can induce the structural diversity of metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A new compound xylarkarynone A (1), a first reported natural product compound xylarkarynone B (2) and eight known compounds (3-10) were isolated from Xylaria sp. HHY-2. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses and electronic circular dichroism (ECD) calculations. The bioactivities of isolated compounds were assayed. Compound 1 exhibited obvious activity against A549 cells with an IC 50 value of 6.12±0.28 μM. Additionally, compound 1 showed moderate antifungal activities against Plectosphaerella cucumerina and Aspergillus niger with minimum inhibitory concentrations (MICs) of both 16 μg/mL, which was at the same grade with positive control nystatin. Most compounds exhibited varying degrees of inhibitory activity against P. cucumerina, indicating that Xylaria sp. has potential as inhibitors against P. cucumerina., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A new alkaloid, neohelicomyine A ( 1 ), along with two known alkaloids ( 2 - 3 ), were isolated from the fermentation of Neohelicomyces hyalosporus PF11-1. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1 D and 2 D NMR, HRESIMS and ECD. The bioactivities of all compounds were evaluated using cellular assays, and compounds 2 and 3 displayed moderate cytotoxicities against human cancer (A549, TCA, RD) cells with IC 50 values of 26-87 μg/mL.

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1-6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1, 3, 4, and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H 2 O 2 -induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS., Competing Interests: Declaration of competing interest On behalf of, and having obtained permission from all the authors, I declare that: a. the material has not been published in whole or in part elsewhere; b. the paper is not currently being considered for publication elsewhere; c. all authors have been personally and actively involved in substantive work leading to the report, and will hold themselves jointly and individually responsible for its content; d. all relevant ethical safeguards have been met in relation to patient or subject protection, or animal experimentation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC 50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Fungi are a source of a variety of secondary metabolites of importance in different areas of biotechnology. Several compounds have been characterized with antioxidant, antimicrobial, and anti-inflammatory activity from fungi of the division of the Ascomycota, among which is the species Daldinia eschscholtzii , an endophyte fungus of pantropical distribution. In this study, we evaluated the effect of an ointment made with D. eschscholtzii on the wound healing of BALB/c mice. The species was corroborated using a molecular marker Internal Transcribed Spacer (ITS1 and ITS4). The extracts and dust of the fungus were considered nontoxic as they caused a mortality of <15% in the nematode Panagrellus redivivus , and experimental ointments had no adverse effects on the skin of BALB/c mice. Wounds treated with the D. eschscholtzii ointments had 99.9-100% wound contraction after 17 days, which was similar to commercial healing (positive control). As such, the ointment of D. eschscholtzii is a natural alternative to improve wound healing.

Arthrobotrys flagrans, a nematode-eating fungus, is an effective component of animal parasitic nematode biocontrol agents. In the dried formulation, the majority of spores are in an endogenous dormant state. This study focuses on dormant chlamydospore and nondormant chlamydospore of A. flagrans to investigate the differences in cyclic adenosine monophosphate (cAMP) and protein content between the two types of spores. cAMP and soluble proteins were extracted from the nondormant chlamydospore and dormant chlamydospore of two isolates of A. flagrans. The cAMP Direct Immunoassay Kit and Bradford protein concentration assay kit (Coomassie brilliant blue method) were used to detect the cAMP and protein content in two types of spores. Results showed that the content of cAMP in dormant spores of both isolates was significantly higher than that in nondormant spores (p < 0.05). The protein content of dormant spores in DH055 bacteria was significantly higher than that of nondormant spores (p < 0.05). In addition, the protein content of dormant spores of the SDH035 strain was slightly higher than that of nondormant spores, but the difference was not significant (p > 0.05). The results obtained in this study provide evidence for the biochemical mechanism of chlamydospore dormancy or the germination of the nematophagous fungus A. flagrans., (© 2024 Wiley‐VCH GmbH.)

The inhibitory properties and underlying mechanism of chlorine dioxide (ClO 2 ) fumigation on the pathogen Ceratocystis fimbriata (C. fimbriata) and resultant sweetpotato black rot were investigated in vitro and in vivo. Results revealed that the ClO 2 fumigation effectively inhibited fungal growth and induced obvious morphological variation of C. fimbriata mycelia. Furthermore, the mycelial membrane suffered damage, as evidenced by a significant increase in malondialdehyde content and the leakage of protein and nucleic acid from mycelia cells, accompanied by a marked decrease in ergosterol content. Additionally, ClO 2 fumigation caused spores cell membrane damage, a notable decrease in spore viability, and induced cell apoptosis as indicated by reductions in spore germination rate, two fluorescence staining observations, and flow cytometry analysis. Moreover, the decay diameter of sweetpotato black rot lesions decreased significantly after ClO 2 fumigation, and the growth of C. fimbriata was also inhibited. These findings present a novel and effective technology for inhibiting the progression of sweetpotato black rot., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

To further reveal the interaction mechanism between plants and pathogens, this study used confocal Raman microscopy spectroscopy (CRM) combined with chemometrics to visualize the biopolymers distribution of kiwifruit cell walls at different infection stages at the cellular micro level. Simultaneously, the changes in the content of various monosaccharides in fruit were studied at the molecular level using high-performance liquid chromatography (HPLC). There were significant differences in the composition of various nutrient components in the cell wall structure of kiwifruit at different infection times after infection by Botryosphaeria dothidea. PCA could cluster samples with infection time of 0-9 d into different infection stages, and SVM was used to predict the PCA classification results, the accuracy >96 %. Multivariate curve resolution-alternating least squares (MCR-ALS) helped to identify single substance spectra and concentration signals from mixed spectral signals. The pure substance chemical imaging maps of low methylated pectin (LMP), high methylated pectin (HMP), cellulose, hemicellulose, and lignin were obtained by analyzing the resolved concentration data. The imaging results showed that the lignin content in the kiwifruit cell wall increased significantly to resist pathogens infection after the infection of B. dothidea. With the development of infection, B. dothidea decomposed various substances in the host cell walls, allowing them to penetrate the interior of fruit cells. This caused significant changes in the form, structure, and distribution of various chemicals on the fruit cell walls in time and space. HPLC showed that glucose was the main carbon source and energy substance obtained by pathogens from kiwifruit during infection. The contents of galactose and arabinose, which maintained the structure and function of the fruit cell walls, decreased significantly and the cell wall structure was destroyed in the late stage of pathogens infection. This study provided a new perspective on the cellular structure changes caused by pathogenic infection of fruit and the defense response process of fruit and provided effective references for further research on the mechanisms of host-pathogen interactions in fruit infected by pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The filamentous fungus Magnaporthe oryzae is widely recognized as a notorious plant pathogen responsible for causing rice blasts. With rapid advancements in molecular biology technologies, numerous regulatory mechanisms have been thoroughly investigated. However, most recent studies have predominantly focused on infection-related pathways or host defence mechanisms, which may be insufficient for developing novel structure-based prevention strategies. A substantial body of literature has utilized cryo-electron microscopy and X-ray diffraction to explore the relationships between functional components, shedding light on the identification of potential drug targets. Owing to the complexity of protein extraction and stochastic nature of crystallization, obtaining high-quality structures remains a significant challenge for the scientific community. Emerging computational tools such as AlphaFold for structural prediction, docking for interaction analysis, and molecular dynamics simulations to replicate in vivo conditions provide novel avenues for overcoming these challenges. In this review, we aim to consolidate the structural biological advancements in M. oryzae , drawing upon mature experimental experiences from other species such as Saccharomyces cerevisiae and mammals. We aim to explore the potential of protein construction to address the invasion and proliferation of M. oryzae , with the goal of identifying new drug targets and designing small-molecule compounds to manage this disease.

To address the lengthy cycles, complex operations, high costs, and insufficient sensitivity of biomarker detection in traditional biological control agents, photonic crystal treated with PEI was developed for highly sensitive detection of Sclerotinia sclerotiorum microbial spores. By incorporating gelatin molecules, photonic crystal is endowed with excellent photothermal stability and high stability in aqueous solutions. The photonic crystal surface is conferred a positive charge by PEI, which can be used to enhance the adsorption of spores. Efficient enrichment of Sclerotinia sclerotiorum and Purpureocillium lilacinum spores is achieved, with coefficients of determination 0.963 and 0.971, respectively. The detection range is from 10 2 to 10 6 spores/ml, and the photonic crystal exhibited good reusability. The prepared photonic crystal enables rapid, non-destructive, and accurate quantitative detection of microbial spores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rhamnolipids (RLs) and Fengycins (FGs) are biosurfactants with very promising antifungal properties proposed to reduce the use of synthetic pesticides in crops. They are amphiphilic molecules, both known to target the plasma membrane. They act differently on Botrytis cinerea and Sclerotinia sclerotiorum, two close Sclerotiniaceae phytopathogenic fungi. RLs are more efficient at permeabilizing S. sclerotiorum, and FGs are more efficient at permeabilizing B. cinerea mycelial cells. To study the link between the lipid membrane composition and the activity of RLs and FGs, we analyzed the lipid profiles of B. cinerea and S. sclerotiorum. We determined that unsaturated or saturated C18 and saturated C16 fatty acids are predominant in both fungi. We also showed that phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylcholine (PC) are the main phospholipids (in this order) in both fungi, with more PA and less PC in S. sclerotiorum. The results were used to build biomimetic lipid membrane models of B. cinerea and S. sclerotiorum for all-atom molecular dynamic simulations and solid-state NMR experiments to more deeply study the interactions between RLs or FGs with different compositions of lipid bilayers. Distinctive effects are exerted by both compounds. RLs completely insert in all the studied model membranes with a fluidification effect. FGs tend to form aggregates out of the bilayer and insert individually more easily into the models representative of B. cinerea than those of S. sclerotiorum, with a higher fluidification effect. These results provide new insights into the lipid composition of closely related fungi and its impact on the mode of action of very promising membranotropic antifungal molecules for agricultural applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bioactivity-based molecular networking-guided fractionation enabled the isolation of three new polycyclic tetramic acids bearing cis -decalin, epicolidines A-C ( 1 - 3 ), along with one known compound, PF 1052 ( 4 ), from the endophytic fungus Epicoccum sp. 1-042 collected in Tibet, China. Their structures were assigned on the basis of extensive spectroscopic data, partial hydrolysis, advanced Marfey's method, quantum chemistry calculations, and X-ray diffraction analysis. Compounds 2 - 4 displayed promising activities against Gram-positive bacteria in vitro . Particularly, compound 4 displayed remarkable potential against vancomycin-resistant Enterococcus faecium (VRE) with an MIC value of 0.25 μg/mL, lower than the MIC (0.5 μg/mL) of the antibiotic combination quinupristin/dalfopristin (Q/D). In a further in vivo study, compound 4 increased the survival rate to 100% in the VRE- G. mellonella infection model at a concentration of 10 mg/kg.

There are >350 species of the Ophiobolus genus, which is not yet very well-known and lacks research reports on secondary metabolites. Three new 3,4-benzofuran polyketides 1-3, a new 3,4-benzofuran polyketide racemate 4, two new pairs of polyketide enantiomers (±)-5 and (±)-7, two new acetophenone derivatives 6 and 8, and three novel 1,4-dioxane aromatic polyketides 9-11, were isolated from a fungus Ophiobolus cirsii LZU-1509 derived from an important medicinal and economic crop Anaphalis lactea. The isolation was guided by LC-MS/MS-based GNPS molecular networking analysis. The planar structures and relative configurations were mainly elucidated by NMR and HR-ESI-MS data. Their absolute configurations were determined by using X-ray diffraction analysis and via comparing computational and experimental ECD, NMR, and specific optical rotation data. 9 possesses an unreported 5/6/6/6/5 five-ring framework with a 1,4-dioxane, and 10 and 11 feature unprecedented 6/6/6/5 and 6/6/5/6 four-ring frames containing a 1,4-dioxane. The biosynthetic pathways of 9-11 were proposed. 1-11 were nontoxic in HT-1080 and HepG2 tumor cells at a concentration of 20 μM, whereas 3 and 5 exerted higher antioxidant properties in the hydrogen peroxide-stimulated model in the neuron-like PC12 cells. They could be potential antioxidant agents for neuroprotection., Competing Interests: Declaration of Competing Interest The authors declare that there is no competing interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC 50 values ranging from 4.4 to 47.4 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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 IC 50 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 IC 50 values of 32.55 ± 1.76 μM, 18.40 ± 1.43 μM, and 27.31 ± 1.22 μM, respectively)., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigated the chemical composition and the antifungal activity of the essential oil extracted from the Hymenaea stigonocarpa fruit peel (HSFPEO) against Botrytis cinerea , Sclerotinia sclerotiorum , Aspergillus flavus and Colletotrichum truncatum . The HSFPEO obtained through hydrodistillation was analyzed with gas chromatography coupled to mass spectrometry. The antifungal activity was determined by the mean mycelial growth inhibition of the fungus treated with essential oils and growth control. The major constituents of HSFPEO were spathulenol (25.19%) and caryophyllene oxide (13.33%). HSFPEO demonstrated antifungal activity against all fungi tested in all concentrations evaluated in a dose-dependent behavior. The best results were observed against B. cinerea and A. flavus , in which the lowest concentration tested inhibited more than 70% of mycelial growth. Based on the current knowledge, this study describes for the first time the chemical composition and the antifungal activity of HSFPEO against the phytopathogenic fungi B. cinerea and C. truncatum .

Six undescribed infrequent eremophilane derivatives including diaportheremopholins A - F and its previously undescribed side chain (E)-2-methyloct-2-enoic acid, together with three known compounds (testacein, xestodecalactones B and C), were isolated from the endophytic fungus Diaporthe sp. BCC69512. The chemical structures were determined based on NMR spectroscopic information in conjunction with the evidence from NOESY spectrum, Mosher's application, and chemical reactions for corroborating the absolute configurations. The isolated compounds were evaluated for biological properties such as antimalarial, anti-TB, anti-phytopathogenic fungal, antibacterial activities and for cytotoxicity against malignant (MCF-7 and NCI-H187) and non-malignant (Vero) cells. Diaportheremopholins B (2) and E (5) possessed broad antimicrobial activity against Mycobacterium tuberculosis, Bacillus cereus, Alternaria brassicicola and Colletotrichum acutatum with MICs in a range of 25.0-50.0 μg/mL. Testacein (7) exhibited strong anti-A. brassicicola and anti-C. acutatum activities with equal MIC values of 3.13 μg/mL. Moreover, diaportheremopholin F (6) and compound 8 displayed antitubercular activity with equal MIC values of 50.0 μg/mL. All tested compounds were non-cytotoxic against MCF-7, NCI-H187, and Vero cells, except those compounds 2 and 5-7 exhibited weak cytotoxicity against both malignant and non-malignant cells with IC 50 values in a range of 15.5-115.5 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of 1 H, 13 C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC 50 values of 1.78 μM and 1.54 μM, respectively. Moreover, they inhibited the secretion of IL-1β and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 M pro ), with IC 50 values of 10.8 ± 0.9 μM and 12.9 ± 0.7 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The discovery of structurally distinct leads is imperative in modern agrochemical science. Inspired by eudistomins Y and the framework-related pharmaceuticals, aryl heteroaryl ketone was drawn as a common model intriguing the design and divergent synthesis of 14 kinds of heteroaryl ketones aligned with their oxime derivatives. Antifungal function-oriented phenotypical screen protruded benzothiazolyl-phenyl oxime 5a as a promising model, and the concomitant modification led to benzothiazolyl oxime 5am (EC 50 = 5.17 μM) as a superior lead than fluoxastrobin (EC 50 = 7.54 μM) against Sclerotinia sclerotiorum . Scaffold hopping of the phenyl subunit identified benzothiazolyl-pyridyl oxime as a novel antifungal scaffold accompanied by acquiring oxime 5bm with remarkable activity (EC 50 = 3.57 μM) against Pyricularia oryzae . Molecular docking showed that candidate 5am could form more hydrogen bonds with the amino acid residues of actin than metrafenone. This compound also demonstrated better curative efficacy than that of fluoxastrobin and metrafenone in controlling the plant disease caused by S. sclerotiorum . These results rationalize the discovery of antifungal candidates based on aryl heteroaryl ketone.

The endolichenic fungi are an unexplored group of organisms for the production of bioactive secondary metabolites. The aim of the present study is to determine the antibacterial potential of endolichenic fungi isolated from genus Parmotrema. The study is continuation of our previous work, wherein a total of 73 endolichenic fungi were isolated from the lichenized fungi, which resulted in 47 species under 23 genera. All the isolated endolichenic fungi were screened for preliminary antibacterial activity. Five endolichenic fungi-Daldinia eschscholtzii, Nemania diffusa, Preussia sp., Trichoderma sp. and Xylaria feejeensis, were selected for further antibacterial activity by disc diffusion method. The zone of inhibition ranged from 14.3 ± 0.1 to 23.2 ± 0.1. The chemical composition of the selected endolichenic fungi was analysed through GC-MS, which yielded a total of 108 compounds from all the selected five endolichenic fungi. Diethyl phthalate, 1-hexadecanol, dibutyl phthalate, n-tetracosanol-1, 1-nonadecene, pyrrol[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl) and tetratetracontane were found to be common compounds among one or the other endolichenic fungi, which possibly were responsible for antibacterial activity. GC-MS data were further analysed through Principal Component Analysis which showed D. eschscholtzii to be with unique pattern of expression of metabolites. Compound confirmation test revealed coumaric acid to be responsible for antibacterial activity in D. eschscholtzii. So, the study proves that endolichenic fungi that inhabit lichenized fungal thalli could be a source of potential antibacterial compounds., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 IC 50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC 50 values of 167.0 μmol/L.