Search Results (347)

Marine natural products have gained increasing interest in drug research and development because of their unique structures, diverse biological activities, and novel mechanisms of action. Using the antiviral alkaloid aldisine as the lead compound and utilizing the hydrogen bond effects common in drug design, novel derivatives containing an acylhydrazone moiety were designed and synthesized. The structures of these derivatives were systematically analyzed using variable-temperature ¹H-NMR. Antiviral activity tests showed that most derivatives were active against tobacco mosaic virus (TMV), with some compounds outperforming the commercial antiviral drug ribavirin. Notably, 3-methylphenyl- and 3-pyridyl-substituted acylhydrazones 5-6 and 5-12 displayed activity comparable to ningnanmycin, one of the most effective commercial antiviral agents. Molecular docking results indicated that incorporating the acylhydrazone moiety enhances hydrogen bonding between the molecules and target proteins. Additionally, we evaluated the fungicidal and larvicidal activities of these derivatives. Most exhibited significant larvicidal effects against Mythimna separata and Plutella xylostella, along with broad-spectrum fungicidal activity. Four related compounds (5-11, 5-12, 5-13, and 5-17) exhibited high fungicidal activities, and another four compounds (2-4, 5-6, 5-13, and 5-17) exhibited high larvicidal activities. Full article

Curvularia lunata (Wakkre) Boedijn is an important pathogenic fungus that causes maize leaf spot, a prevalent disease that caused significant yield losses in maize-growing areas in China in the 1990s. Clpks18, a polyketide synthase (CLPKS18) gene, has been identified as a crucial virulence-related gene in C. lunata. However, the impact of Clpks18 and its biosynthesized virulence factor (R)-(-)-mellein on the expression of maize genes related to the defense signal pathway has never been determined. In this study, it was found that Clpks18 and (R)-(-)-mellein significantly interfere with the signaling pathways of JA and IAA in maize leaves but in different ways and in a time-dependent manner. While CLPKS18 inhibited the maize’s JA and IAA signaling pathways through its related secondary metabolite, (R)-(-)-mellein inhibited the JA signaling pathway but stimulated IAA accumulation in maize leaves. In summary, understanding this novel virulence effector’s mechanism of interference with maize resistance enriches the pathology of Curvularia leaf spot in maize on the one hand and provides a foundation for screening the resistance germplasm and chemical fungicides against the disease on the other. Full article

Strawberry (Fragaria x ananassa) production has increased around the world, but crop quality and yield are threatened by fungal pathogens. Botrytis cinerea is a filamentous fungus that infects over 1400 species of crops, causing gray mold disease with devastating losses to horticulture worldwide, including strawberry. The heavy reliance on synthetic fungicides in the strawberry industry has led to the emergence of fungicide resistance in B. cinerea. Therefore, understanding the fundamental biology of B. cinerea is an important step in the search for novel antifungals. Although B. cinerea is one of the most serious pathogens of strawberry, this pathosystem is understudied compared to other plant hosts. Consequently, further evidence is needed on pathogen penetration and early disease development in strawberry tissues. Here, we adapted and advanced assays using detached strawberry leaves, fruits, and petals to study B. cinerea infection. These assays allow the comparison of the treatment effect on the same fruit, avoiding confounding from differential ripening, and facilitate the screening of fungicides or biocontrol agents. Through chlorophyll fluorescence analysis and scanning electron and confocal microscopy, we quantified lesions caused by B. cinerea in the early stages of infection in fruit and petals, and demonstrated that B. cinerea penetrates through the stomata of strawberry achenes, revealing a previously unrecognized infection route in this host. These data provide a deeper understanding of the B. cinerea–strawberry interaction and will serve as a foundation for future studies seeking novel antifungal treatments against B. cinerea. Full article

In November 2022, black-root and stem-rot symptoms were observed on the strawberry cultivar ‘Ssanta’ in Hohhot, Inner Mongolia Autonomous Region, China. In order to identify the causing agent of strawberry root rot, and select effective fungicides for controlling this disease, this study was carried out. The associated fungi were isolated from diseased strawberry plants, and the isolate that fulfilled Koch’s postulates was further identified based on morphological characteristics, together with the internal transcribed spacer regions and 28S rDNA sequences; then, the inhibitory activities of 11 commercial fungicides on the pathogenic strain were screened based on the mycelium growth method. Results showed that six candidate strains were isolated from diseased strawberry, and only the isolate CMGF-A caused typical root and stem rot on strawberry. The CMGF-A showed typical morphology of Acrostalagmus species, and sequence analyses revealed it as A. luteoalbus. The prochloraz was selected as the primary fungicide for effectively controlling CMGF-A, while tebuconazole, thiophanate-methyl, and difenoconazole·azoxystrobin could be used as alternatives. A. luteoalbus was previously reported to cause potato tuber disease, and red rust of needle mushroom, this work is the first report of A. luteoalbus causing strawberry root rot worldwide. This study provided helpful information for the diagnosis and management of strawberry root rot disease. Full article

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release. Full article

Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus Fusarium. This situation threatens yield and grain quality through root and crown rot. While conventional chemical fungicides face resistance issues and environmental concerns, biological alternatives like seed priming with natural metabolites are gaining attention. Polyamines, including putrescine, spermidine, and spermine, are attractive priming agents influencing plant development and abiotic stress responses. Spermine in particular shows potential for in vitro antifungal activity against Fusarium. Optimising spermine concentration for seed priming is crucial to maximising protection against Fusarium infection while ensuring robust plant growth. In this research, we explored the potential of the polyamine spermine as a seed treatment to enhance wheat resilience, aiming to identify a sustainable alternative to synthetic fungicides. Our findings revealed that a six-hour seed soak in spermine solutions ranging from 0.5 to 5 mM did not delay germination or seedling growth. In fact, the 5 mM concentration significantly stimulated root weight and length. In complementary in vitro assays, we evaluated the antifungal activity of spermine (0.5–5 mM) against three Fusarium species. The results demonstrated complete inhibition of Fusarium culmorum growth at 5 mM spermine. A less significant effect on Fusarium graminearum and little to no impact on Fusarium oxysporum were found. The performed analysis revealed that the spermine had a fungistatic effect against the pathogen, retarding the mycelium growth of F. culmorum inoculated on the seed surface. A pot experiment with Bulgarian soft wheat cv. Sadovo-1 was carried out to estimate the effect of seed priming with spermine against infection with isolates of pathogenic fungus F. culmorum on plant growth and disease severity. Our results demonstrated that spermine resulted in a reduced distribution of F. culmorum and improved plant performance, as evidenced by the higher fresh weight and height of plants pre-treated with spermine. This research describes the efficacy of spermine seed priming as a novel strategy for managing Fusarium root and crown rot in wheat. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Strobilurins are a prominent class of fungicides capable of entering aquatic environments via runoff and leaching from the soil. Findings from previous studies suggest that strobilurins are highly toxic in aquatic environments, and evidence of acute developmental toxicity and altered behavioral responses have been emphasized. The objective here was to determine the effects of a new strobilurin, metyltetraprole (MTP), on zebrafish using developmental endpoints, gene expression, and behavioral locomotor assays. We hypothesized that MTP would cause developmental toxicity and induce hyperactivity in zebrafish (Danio rerio). To test this, developing zebrafish embryos/larvae were exposed to environmentally relevant levels of MTP (0.1, 1, 10, and 100 µg/L) until 7 days post-fertilization. Survival percentages did not differ among the treatment groups. No change in reactive oxygen species production was detected, but two genes involved in the mitochondrial electron transport chain (mt-nd3 and uqcrc2) were altered in abundance following MTP exposure. Moreover, the highest concentration (100 µg/L) of MTP caused notable hyperactivity in the zebrafish in the visual motor response test. Overall, results from this study increase our knowledge regarding sub-lethal effects of MTP, helping inform risk assessment for aquatic environments. Full article

Artemisia serotina Bunge represents one of the endemic Artemisia L. species in flora of Central Asia. There is scant information on the phytochemistry and biological activity of this species. The aim of the present study was to analyze the chemical composition of essential oil from A. serotina (ASEO) growing in south Kazakhstan, together with the determination of its biological activity. ASEO isolation was carried out by hydrodistillation according to the State Pharmacopoeia of the Republic of Kazakhstan. Analysis of GC/MS data revealed that the most characteristic components of ASEO were irregular monoterpenes from three families: santolinane, artemisane, and lavandulane. The major compound was santolina alcohol (34.6%). Antimicrobial activity was studied against the reference bacterial and fungal strains using the recommended methods, allowing for an estimation of MIC (minimum inhibitory concentration). ASEO was most effective against Candida albicans (MIC = 2 mg/mL), exerting fungicidal activity. Thw MIC for bacterial species was higher, i.e., 4–16 mg/mL. Antiviral activity was tested against Coxsackievirus B3 (CVB3) and Human Herpesvirus type 1 (HHV-1) propagated in VERO cells. No antiviral effect against either virus was found at an ASEO concentration of 0.25 mg/mL, but a noticeable decrease in the intensity of HHV-1-related cytopathic effects was observed. Anticancer activity studies included several cancer cell lines. Cytotoxicity, cell cycle, thiol levels, and cell vitality were analyzed. Among the cancer cell lines tested, the breast cancer T47-D cell line exhibited the highest sensitivity to ASEO (IC₅₀ = 40.81 ± 4.21 µg/mL at 24 h; IC₅₀ = 33.17 ± 2.11 µg/mL at 48 h). The anticancer effect was suggested to be mainly due to the induction of cytostatic effects, accompanied by a disturbance of the intracellular redox balance. The obtained data provide novel information on the unique chemical composition of ASEO from south Kazakhstan, representing a new chemotype. Its bioactivity, including promising antifungal and anticancer properties, was demonstrated for the first time. Full article

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using Artemisia absinthium L. extract has gained considerable attention due to its eco-friendly approach and potential applications in food science. This study investigates the synthesis and characterization of Artemisia-mediated ZnO NPs, focusing on their physicochemical properties. The nanoparticles were characterized using ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (EDX). Successful synthesis was achieved through a co-precipitation method, resulting in an average particle size of 36.6 nm. The presence of polyphenols and flavonoids in A. absinthium L. extract acted as both a reducing agent and stabilizer for the nanoparticles. The physicochemical characterization revealed strong absorption peaks indicative of ZnO, confirming successful nanoparticle formation. In addition to the structural findings, this study presents novel insights by demonstrating that Artemisia-mediated ZnO NPs possess significantly enhanced antimicrobial activity compared to both pure ZnO NPs and the plant extract alone. The biosynthesized nanoparticles exhibited notably lower minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values against Staphylococcus aureus, Escherichia coli, and Candida albicans, suggesting a strong synergistic effect between ZnO and the phytochemicals of A. absinthium L. Thus, the study confirms and quantifies the superior antibacterial potential of Artemisia-derived ZnO NPs, offering promising implications for food, biomedical and pharmaceutical applications. Full article

Mycogone perniciosa is the causative agent of wet bubble disease, which induces significant losses in the production of Agaricus bisporus, indicating the high importance of the development of novel inhibitory agents. The isolation, identification, and molecular characterization of five isolates of M. perniciosa from diseased fruit bodies of A. bisporus was done. Moreover, the study evaluated the in vitro and in situ potential of Origanum vulgare essential oil (EO) to limit M. perniciosa growth and provided chemical characterization of its volatile components. The obtained strains differed phenotypically and according to their molecular characteristics. O. vulgare EO has shown more promising antifungal activity than the commercial fungicide Prochloraz-Mn in the microatmospheric method. In the treatment of experimentally induced wet bubble disease on A. bisporus in the growing chambers with 2% of O. vulgare EO and simultaneous application of spore suspension of mycopathogen, O. vulgare EO totally inhibited the growth of M. perniciosa. Carvacrol, p-cymene, γ-terpinene, and thymol were dominant constituents of O. vulgare EO examined in this study. O. vulgare EO has shown promising potential to limit growth of M. perniciosa and should be further explored as a novel biofungicide. Full article

Nine chaetoglobosins (1–9) including five previously undescribed ones (1–5) were obtained from the culture broth of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites were elucidated by spectroscopic methods including mass spectroscopy, nuclear magnetic resonance, single crystal X-ray crystallography, and electronic circular dichroism. To accelerate the development of novel fungicides, all of the isolated chaetoglobosins were evaluated for their antifungal activity against two crop pathogens, Botrytis cinerea and Sclerotinia sclerotiorum. The assay results revealed that chaetoglobosins 2, 6, 7, and 9 possessed a significant fungicidal effect against B. cinerea, with EC₅₀ values all below 10 μg/mL. Particularly, the most potent compound, 7, was 175- and 96-fold as active as the commercially available fungicides carbendazim (EC₅₀ 70.11 μg/mL) and azoxystrobin (EC₅₀ 39.02 μg/mL), respectively. A further observation under scanning electron microscope indicated that compound 2 could markedly impair the fungal hyphae of B. cinerea. The study demonstrates that the chaetoglobosins had excellent in vitro antifungal activities against B. cinerea. Full article

To identify fungicide lead compounds with novel scaffold and high efficacy, a library of 4,5-dihydrotetrazolo [1,5-a]thieno [2,3-e]pyridine derivatives, consisting of 10 newly synthesized compounds and 12 previously reported compounds, was evaluated for their potential as fungicide agents. In vitro bioassay results indicated that some target compounds exhibited certain antifungal activity against the tested fungi at a concentration of 50 μg/mL. Especially, compounds I-1, I-5, I-7, and I-12 demonstrated promising antifungal activity against C. arachidicola, R. solani, and S. sclerotiorum, with EC₅₀ values ranging from 4.61 to 6.66 μg/mL. Additionally, transcriptome analysis revealed that the molecular mode of action of compound I-12 involves the inhibition of nitrogen metabolism and the proteasome pathway. The present work demonstrates that 4,5,6,7-tetrahydrothieno [3,2-b] pyridine represents a promising lead scaffold and provides important theoretical foundations and innovative perspectives for the development of novel and highly efficient fungicides. Full article

Background/Objectives: Endophytic fungi are valuable sources of bioactive compounds with potential therapeutic applications. This study aimed to evaluate the antifungal activity of secondary metabolites produced by Fusarium sp. isolated from Dizygostemon riparius, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. Methods: The fungus was cultivated in standard Czapek medium and media supplemented with NH₄Br or MnCl₂. Methanolic extracts were obtained, fractionated, and chemically characterised via LC-ESI-HRMS. In vitro antifungal assays, including MIC and MFC determinations and biofilm inhibition tests, were performed against Candida albicans strains. In vivo toxicity and efficacy were assessed using Tenebrio molitor larvae. Results: Fifteen metabolites were annotated, including known antifungals such as fusaric acid and cyclosporin A. Fractions EMBr4 and EMC5 demonstrated fungicidal activity with MIC values close to fluconazole and significantly inhibited biofilm formation and maturation. In vivo, these fractions displayed low acute toxicity and improved survival in infected larvae, comparable to fluconazole treatment. Conclusions: The results indicate that culture medium modulation enhances the production of bioactive metabolites by Fusarium sp., leading to extracts with notable antifungal efficacy and safety. EMBr4 and EMC5 are promising candidates for further development as antifungal agents, particularly for targeting biofilm-associated Candida infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations. Full article