Search Results (3,064)

Neurodegenerative diseases are a serious problem for modern society, and their treatment remains an important issue discussed by the scientific community. One of the promising potential directions for modulating neurodegenerative processes is the use of acylhydrazones, a class of compounds that combine different bioactive fragments linked by an acylhydrazone moiety. So far, the biological properties of these compounds have been proven. They show antibacterial, antiviral, antifungal, antiparasitic, anticancer, anti-inflammatory and antioxidant activity. Many research papers focus on designing acylhydrazones that will find use in the treatment of neurodegenerative diseases by inhibiting the enzymatic activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase 1 (BACE1) and monoamine oxidase (MAO), as well as inhibiting β-amyloid aggregation, exhibiting metal chelation and antioxidant properties. Recent studies have described the acylhydrazone-based dual (multi-target) inhibitors, which have demonstrated encouraging outcomes during in vitro evaluations. This review covers recent articles published in the years 2020–2025 and offers a comprehensive overview of the biological properties of the acylhydrazones and their multifunctional derivatives on neurodegenerative processes and/or neuroprotection, while emphasizing their universal nature, structural versatility and role as leading structures in the search for new drugs. Full article

The increasing demand for sustainable plant protection products has intensified interest in microbial biocontrol agents (BCAs). This study aimed to evaluate the antifungal activity of selected Streptomyces, Bacillus, and Trichoderma asperellum strains against phytopathogenic fungi and to assess their potential as BCAs under in vitro conditions. The antifungal activity of ten Streptomyces strains was first evaluated against Botrytis cinerea, Colletotrichum salicis, Fusarium oxysporum, and F. graminearum using a dual-culture assay. All isolates exhibited antifungal activity, with Streptomyces venezuelae MSCL 350 showing the strongest inhibition. In addition, the antifungal activity of T. asperellum MSCL 309 and three Bacillus strains was assessed against twelve Fusarium spp. isolates obtained from oats. T. asperellum demonstrated broad-spectrum inhibition, with growth inhibition ranging from 44.6% to 78.4%, primarily due to soluble metabolites, while volatile compounds showed no significant effect. Among the other tested Bacillus strains, only Bacillus subtilis MSCL 1441 exhibited antifungal activity, inhibiting all tested isolates. These results demonstrate strong strain-dependent antifungal activity and highlight T. asperellum MSCL 309, S. venezuelae MSCL 350, and B. subtilis MSCL 1441 as promising candidates for the development of environmentally friendly biocontrol agents. Full article

Propolis is a bee product with a complex chemical composition that exhibits remarkable antifungal activity against C. albicans and can inhibit resistant biofilms thanks to its content of compounds such as flavonoids and phenolic acids. Its efficacy varies depending on its geographic origin: European propolis inhibits the initial formation of biofilms, while Brazilian propolis is superior at inhibiting mature biofilms. This product also possesses fungicidal and fungistatic properties comparable in efficacy to conventional drugs, such as nystatin, fluconazole, and chlorhexidine. The use of nanotechnology, such as nanoparticles or nanorods, has overcome the low solubility of propolis compounds, improving their bioavailability and reducing cell adhesion and hyphal formation. Moreover, the integration of propolis into dental materials demonstrate its versatility for preventing recurrent infections. The study of isolated compounds such as pinocembrin, galangin, and chrysin has facilitated the identification of specific mechanisms of action, and the application of molecules such as guttiferone E in photodynamic therapies and the discovery of quorum-sensing inhibitors, such as kaempferol, using in silico models have opened new avenues for blocking yeast communication and virulence. These findings position propolis as a multifaceted and promising therapeutic alternative, although there is a need to optimize formulations to ensure clinical safety and biocompatibility. In this review, we analyze research published around the world over the last 15 years on the effects of propolis against C. albicans biofilms. Full article

Candida albicans (C. albicans) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly under conditions of dysbiosis or immunosuppression. Treatment remains challenging due to increasing multidrug resistance. This study investigates the in vitro antifungal potential of Viroelixir, a standardized polyphenol blend derived from green tea and pomegranate and enriched in catechins (including epigallocatechin gallate, EGCG), ellagitannins (notably punicalagin), ellagic acid, and flavonoids, with particular focus on its potential anti-virulence mechanisms. Methods: The effect of Viroelixir on C. albicans growth was assessed using MTT assay, optical density measurements, colony formation, carbohydrate quantification, and pH variation analysis. Biofilm formation, morphological transition, ROS production, necrosis, virulence gene expression, adhesion, and host immune responses were also evaluated. Results: Viroelixir significantly inhibited C. albicans growth and reduced colony formation compared with untreated controls. The formulation also inhibited biofilm formation and markedly reduced pseudohyphal development, reaching up to 94% reduction under specific treatment conditions. Flow cytometry analysis showed an increase in dead fungal cells, reaching approximately 88% following exposure to Viroelixir at the highest tested concentration. In addition, Viroelixir reduced the transcript levels of several virulence-associated genes, including SAP1–SAP9 and EAP1. In epithelial cell co-culture models, pre-treatment of C. albicans with Viroelixir reduced fungal adhesion and attenuated epithelial inflammatory responses, including IL-6, IL-8, and hBD-2 production, and was associated with reduced activation of the TLR4-NF-κB signaling pathway. Conclusions: These findings suggest that the antifungal and anti-virulence effects observed may be associated with the polyphenolic compounds present in the Viroelixir formulation, highlighting its potential as a promising in vitro antifungal candidate against C. albicans. Full article

Fusarium oxysporum f. sp. lycopersici (FOL) is one of the most destructive soil-borne pathogens affecting tomato production worldwide, causing substantial yield losses and persisting in soil for extended periods. The increasing regulatory restrictions on chemical fungicides and the emergence of resistant pathogen strains have intensified the search for sustainable and environmentally friendly alternatives. This systematic review synthesizes studies published between 2000 and 2025 that evaluated the antifungal efficacy of essential oils (EOs), their bioactive constituents, and EO-based nanoformulations against FOL in tomato. A total of 40 studies were included, following the PRISMA 2020 guidelines, encompassing in vitro, greenhouse, and limited field evaluations. Many EOs rich in phenolic compounds and oxygenated monoterpenes, such as thymol, carvacrol, eugenol, citral, and menthol, consistently inhibited FOL growth and spore germination, with reported mycelial growth inhibition ranging from 60 to 100% and minimum inhibitory concentrations (MICs) between 0.05 and 1.5 µL ml⁻¹. However, the use of EOs is often limited because they evaporate quickly, do not mix well with water, can harm plants, and do not persist under field conditions. Nano-delivery systems, including nanoemulsions, polymeric nanoparticles, chitosan-based carriers, and lipid-based nanostructures, have been shown to enhance the stability, bioavailability, and antifungal efficacy of EOs. This has led to improved disease management and reduced pesticide application rates. In addition, several EO-based treatments have been reported to activate plant defense responses, including the induction of defense-related genes, antioxidant enzymes, and epigenetic modifications. Overall, EO-based nanoformulations show promise as next-generation biopesticides for the sustainable management of tomato Fusarium wilt. Nevertheless, large-scale field validation, standardized formulation protocols, and regulatory assessments are required before these technologies can be widely implemented in agriculture. Full article

Three novel alkaloids, penicitrioids A–C (1–3), and two known compounds (4–5) were isolated from the ethyl acetate (EtOAc) extract of the solid fermentation of Penicillium citrinum VDL118, an endophytic fungus harbored in the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub native to the southwestern regions of China, Myanmar, and Vietnam. Compounds 1 and 2 are novel pyridine alkaloids characterized by an unprecedented dihydrofuro[3,4-c]pyridine core, while 3 features a distinct pyrrolo[3,4-c]pyridine framework. Their structures were unambiguously established by comprehensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In vitro antifungal assays revealed that compounds 1–5 exhibited moderate to potent inhibitory effects against five tested phytopathogenic fungi, with minimum inhibitory concentrations (MICs) ranging from 3.1 to 100 μg/mL. Notably, four of them (1–4) displayed broad-spectrum and potent activity against Gloeophyllum trabeum, Coriolus versicolor, Fusarium solani, and Botrytis cinerea, with MIC values as low as 3.1–12.5 μg/mL. Furthermore, a plausible biosynthetic pathway for compounds 1–3 was proposed. Full article

Plant fungal diseases, such as apple tree canker caused by Valsa mali, have caused severe losses in agricultural production. Traditional chemical fungicides induce drug resistance in pathogens and cause environmental pollution. Therefore, it is of substantial importance to screen efficient and environmentally friendly bacterial strains as potential biocontrol agents. The tea rhizosphere harbors abundant microbial resources, and previous research has identified microorganisms with antifungal activity existing in this environment. Therefore, in this study, we isolated antagonistic bacteria with broad-spectrum biocontrol potential from tea rhizosphere soil. In this study, a strain with strong antagonistic activity against V. mali was isolated from tea rhizosphere soil. Based on morphological characteristics, 16S rRNA gene sequencing, and whole-genome analysis, the isolated strain was identified as Bacillus velezensis and designated as LW-66. This strain demonstrated broad-spectrum antifungal activity against various plant pathogenic fungi, including Valsa mali, Fusarium graminearum, Bipolaris sorokinianum, Alternaria solani, and Exserohilum turcicum. The active extract of B. velezensis maintained strong stability across a wide range of temperatures (25–90 °C) and pH values (2–8), with stability decreasing only when the temperature reached 100 °C or pH ≥ 10. In a preventive assay using detached apple branches inoculated with V. mali, the control efficacy of LW-66 against apple tree canker reached more than 90%. Additionally, in a therapeutic assay using V. mali-infected potted apple seedlings, the LW-66 bone-glue bacterial agent achieved a survival rate of up to 90%. Whole-genome analysis revealed that the genome of LW-66 contains 13 predicted secondary metabolite biosynthetic gene clusters, seven of which showed high homology (≥92% similarity) with known antimicrobial gene clusters, including surfactin, bacillaene, macrolactin H, fengycin, difficidin, bacillibactin, and bacilysin. These gene clusters may be connected to the broad-spectrum antifungal activity of B. velezensis, as well as its ability to disrupt hyphal morphology. The volatile organic compounds produced by LW-66 inhibited V. mali growth by 91.70%. Collectively, these findings demonstrate that B. velezensis LW-66 has a wide antimicrobial range and strong antagonistic effects against multiple plant pathogenic fungi. Therefore, B. velezensis shows promise as a biocontrol agent for managing fungal diseases in plants, providing a basis for developing LW-66-derived biocontrol products aimed at controlling diseases such as apple tree canker. Full article

During 2022–2023, research groups from 40 nations contributed to the preclinical pharmacology of 173 structurally defined marine-derived compounds, unveiling innovative mechanisms of action. Peer-reviewed publications in the field of marine natural product pharmacology during 2022–2023 included mechanism-of-action studies with 43 compounds showing antibacterial, antifungal, antiprotozoal, antitubercular, and antiviral activity. Additional mechanism-of-action studies were reported for 74 marine compounds that exhibited antidiabetic and anti-inflammatory properties, as well as significant effects on both the immune and nervous systems. Finally, while 65 marine compounds revealed unique and diverse pharmacological mechanisms, further investigation will be required to determine whether they will contribute to a particular therapeutic category. Collectively, the pharmacology of 2022–2023 preclinical marine natural products demonstrated robust activity, offering both novel mechanistic insights and promising chemical scaffolds to enrich the 2026 marine pharmaceutical development pipeline (https://www.marinepharmacology.org/) which currently consists of 17 marine-derived pharmaceuticals approved for clinical use and 29 compounds in either Phase I, II or III of clinical pharmaceutical development. Full article

Mango (Mangifera indica L.), being a climacteric fruit, is highly perishable due to rapid ripening and post-harvest diseases like anthracnose, which significantly shorten its shelf life and limit long-distance sea export. To mitigate these constraints, a chemical-free secondary metabolite-based formulation (SMsF) was developed to delay ripening and control post-harvest anthracnose during storage. The SMsF possesses dual-action properties and is derived from the culture filtrate of Priestia aryabhattai, exhibiting ACC deaminase activity that restricts ethylene formation. It is also rich in antifungal compounds such as vanillic acid, hydroxybenzoic acid, cryptochlorogenic acid, palmitic acid, and BBIT, which inhibit anthracnose development. Additionally, it contains antioxidants including quercetin, coumaryl quinic acid, oleic acid, and acetylglycitin that enhance shelf life and disease resistance. The efficacy of SMsF was evaluated in mango cv. Banganapalli was stored at 12 ± 1 °C and 85–90% relative humidity under simulated reefer conditions (SRC). Integration of gamma irradiation with SMsF provided superior results in disease control and shelf-life extension. The combined treatment maintained higher fruit firmness (0.86 kg cm⁻²), optimal total soluble solids (14.3 °B), desirable acidity (0.22%), and complete suppression of anthracnose (PDI = 0) up to 40 days of storage under SRC compared with the control. The findings conclusively demonstrate that the synergistic application of SMsF and gamma irradiation effectively regulates ripening, enhances fruit quality, and ensures complete disease suppression, thereby significantly extending storage life. This approach holds strong scientific and commercial significance as a sustainable, residue-free, and export-oriented technology capable of improving long-distance transportation, reducing post-harvest losses, and promoting safe mango trade. Full article

Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant pathogens undermining the effectiveness of conventional antibiotics. Natural alkaloids, a diverse group of nitrogen-containing compounds mainly derived from plants, are gaining attention as potential antimicrobial agents due to their broad-spectrum activity, structural variety, and unique mechanisms of action. This review examines the antimicrobial properties of natural alkaloids, classifying them by chemical structure (e.g., quinoline, isoquinoline, pyridine, indole, and imidazole alkaloids). Their antibacterial, antifungal, and antiviral activities are discussed, along with the mechanisms by which they target pathogenic microorganisms, including disruption of cell walls and membranes, inhibition of protein synthesis, interference with DNA replication, and viral assembly. The review also explores the synergistic effects of alkaloids when combined with conventional antimicrobial agents. Alkaloids demonstrate potent antimicrobial activity against various pathogens. Quinoline alkaloids, such as quinine, inhibit DNA replication and damage cell membranes. Isoquinoline alkaloids like berberine and sanguinarine exhibit broad-spectrum antibacterial effects. Pyridine alkaloids, including nicotine, disrupt bacterial membranes. In fungi, alkaloids such as sanguinarine and indole derivatives prevent cell wall synthesis and spore germination. Antiviral alkaloids like lycorine target viral RNA polymerases. Additionally, alkaloids enhance the activity of traditional antibiotics by overcoming resistance. Natural alkaloids represent a promising source of antimicrobial agents with diverse mechanisms to combat AMR. Future research should focus on optimizing alkaloid structures, ensuring safety and efficacy, and exploring combination therapies to address the escalating AMR challenge. Full article

In this study, potential fungicides were prepared following the principles of green chemistry. The compounds were synthesized in deep eutectic solvents as an alternative medium and compared with syntheses in traditional solvents such as ethanol. The efficiency of the reaction was improved by ultrasonic synthesis in both eutectic solvents and ethanol, resulting in higher yields while reducing reaction energy and time. For the first time, deep eutectic solvents (DES) were used for quaternisation reactions, with choline chloride as a hydrogen bond acceptor and urea, glycerol, malic acid, malonic acid, and levulinic acid as donors. DES, composed of biodegradable, non-toxic, and renewable components, represented a greener alternative to conventional solvents. However, reactions in DES by the conventional method generally resulted in lower yields, probably due to solubility and viscosity limitations inherent in the eutectic medium. The combination of ultrasound and deep eutectic solvents proved to be a good alternative to organic solvents for the quaternisation reaction, as higher yields were achieved in a shorter time compared to conventional methods. The antifungal activity of all 18 synthesized compounds was tested. The compounds exhibited significant antifungal activity against all four pathogens, with varying levels of mycelial growth inhibition. B. cinerea was the most sensitive species (up to 70.7% inhibition), while F. culmorum was the least sensitive (≤32%). Full article

Phenyllactic acid (PLA), a natural antimicrobial metabolite produced by lactic acid bacteria (LAB), has emerged as a key compound for biopreservation in food systems. The aims of this review are to summarize the main findings on LAB-producing strains, the effects of primary PLA precursors, the impacts of culture conditions on PLA production, antimicrobial activity, mechanisms of action, quantification and analysis methods, food applications, regulatory status, and the challenges in PLA production and applications. In this review, the quorum sensing role in PLA production and multi-omics strain improvement was revised. Applications in dairy, bakery, fruits, vegetables, meat, and fish products as well as active packaging are analyzed, demonstrating their effectiveness in controlling microbial spoilage and pathogens while preserving sensory quality. Its broad-spectrum antifungal and antibacterial activities make it particularly attractive as a clean-label alternative to synthetic preservatives, contributing to both food safety and extended shelf life. Finally, current limitations and future research needs are outlined, particularly in optimizing PLA production and establishing its role as a sustainable and effective tool for food safety management. Full article

Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (Fon), severely restricts the sustainable development of the global watermelon industry. While conventional chemical fungicides of this disease have triggered prominent ecological issues, Bacillus-based microbial biocontrol, which combines inherent environmental compatibility with stable control efficacy, has emerged as a key green alternative to chemical management. However, the biocontrol potential of Bacillus sonorensis against this disease has not yet been fully investigated. In this study, we isolated 56 bacterial strains from healthy watermelon rhizosphere soil, and obtained a Fon-antagonistic strain A-5 with the strongest activity (70.15% mycelial inhibition rate), which was identified as B. sonorensis via polyphasic taxonomic analysis. In vitro assays showed that the sterile fermentation filtrate of strain A-5 had a maximum 81.05% inhibition rate against Fon, and its volatile organic compounds also significantly suppressed Fon growth, with broad-spectrum antifungal activity against four common phytopathogenic fungi. Functional tests confirmed that strain A-5 could secrete cell wall-degrading enzymes, produce siderophores and synthesize indole-3-acetic acid, and 17 antimicrobial secondary metabolite biosynthetic gene clusters were identified in its genome. Pot experiments verified that strain A-5 had a 78.04% relative control efficacy against watermelon Fusarium wilt, which significantly reduced seedling disease incidence and upregulated defense-related antioxidant enzyme activities in watermelon leaves. In general, B. sonorensis A-5 is a promising novel biocontrol agent for green management of watermelon Fusarium wilt. Full article

The purpose of this study was to assess the effectiveness of two nanostructures (MgO and Zn/MgO) against Sclerotinia sclerotiorum, which causes white mold disease in peas, as direct antifungal agents or resistance inducers in pea plants. The direct antifungal activity of these nanostructures was evaluated by assessing their ability to inhibit S. sclerotiorum growth in vitro and reduce white mold severity in the greenhouse. The induction of resistance in pea plants was examined by assessing the expression of three defense-related genes using quantitative real-time PCR and measuring the phenolic compounds content in treated pea plants relative to untreated controls. The effect of the tested control agents on the growth and yield of pea plants was investigated. In comparison to the untreated control, S. sclerotiorum growth was markedly suppressed following treatment with the investigated compounds. The complete suppression (100%) of S. sclerotiorum growth was achieved with concentration levels of 100 mg/L for both MgO and Zn/MgO nanostructures. In greenhouse conditions, pea plants treated with the investigated chemicals showed a considerable reduction in the severity of white mold disease when compared to the untreated control plants. The transcript levels of 12-oxophytodienoate reductase 11 (OPR1), antioxidant peroxide (PsOXII), and chlorophyll a-b binding protein genes increased significantly in treated plants with MgO (3.1, 2.7, and 3.5-fold), fungicide (3.2, 2.8, and 2.8-fold), and Zn/MgO (3.5, 3, and 5-fold) compared to control, respectively. Pea plants treated with the tested nanoparticles generated more phenolic content than untreated controls. The application of fungicide and tested nanoparticles to peas greatly enhanced their growth properties. In light of our results, the application of these nanoparticles may represent a novel approach for controlling this pathogen. Full article

Oral fungal infections resulting from non-albicans Candida species and new opportunistic yeasts are increasingly linked to antifungal resistance, especially in individuals with periodontal disease. Bioactive compounds may serve as potential alternatives; nevertheless, there is a paucity of research that has comprehensively assessed their antifungal and antibiofilm efficacy against clinically defined oral yeast isolates. This study aimed to (i) describe the variety and antifungal resistance profiles of oral yeasts isolated from women with various periodontal diseases; (ii) assess four ethanolic extracts of Aseer medicinal plants (Foeniculum vulgare, Solanum incanum, Forsskaolea tenacissima, and Abutilon pannosum) for their antifungal and antibiofilm properties; and (iii) correlate phytochemical composition determined by GC–MS with biological activity. Oral samples (saliva and subgingival plaque) were collected from 50 female participants with documented periodontal parameters. Fungal isolates were identified using morphological, biochemical (VITEK 2), and molecular (ITS rDNA sequencing) methods. Testing for antifungal susceptibility was performed according to CLSI guidelines. Plant extracts were evaluated for antifungal activity (disk diffusion, MIC, MFC), antibiofilm activity (crystal violet assay and light microscopy), and phytochemical profiling (GC–MS). Fungal growth was detected in 37 of 50 samples (74%), yielding six yeast species: Nakaseomyces glabratus (40.5%), Candida tropicalis (18.9%), C. parapsilosis (13.5%), Pichia kudriavzevii (10.8%), Rhodotorula mucilaginosa (8.1%), and Aureobasidium melanogenum (8.1%). N. glabratus demonstrated reduced susceptibility to fluconazole. A. pannosum and F. vulgare exhibited the strongest in vitro antifungal activity (inhibition zones up to 19.2 mm; MIC 0.19–0.78 mg/mL; MFC 0.39–1.56 mg/mL), significantly greater than F. tenacissima (p < 0.0001). Sub-MIC concentrations of A. pannosum reduced C. tropicalis biofilm biomass by 59.6%. GC–MS analysis identified methyl salicylate (20.3–40.2%) and cyclohexanol derivatives (8.0–23.2%) as major constituents. Antifungal activity showed a trend in relation to methyl salicylate content (R² = 0.78). However, because only four plant extracts were included, this relationship should be interpreted as a descriptive observation rather than a statistically testable association. Ethanolic extracts of Abutilon pannosum and Foeniculum vulgare demonstrated significant in vitro antifungal and antibiofilm activity against clinically relevant oral yeasts, including azole-tolerant Nakaseomyces glabratus. The observed trends between phytochemical composition and biological activity warrant further investigation into their potential as adjunct therapeutic agents for oral fungal infections. Further studies are required to confirm these results and see if they can be used in therapeutic settings. Full article