Search Results (2,466)

Pteridium aquilinum (L.) Kuhn, known as bracken fern, is considered a poisonous plant due to its toxic substances. This species contains toxic substances and enzymes: thiaminase and an anti-thiamine substance, which cause thiamine deficiency syndrome. Prunasin induces acute cyanide poisoning. Ptaquiloside causes haematuria, retinal atrophy, immunodeficiency, and lymphoproliferative disorders. It also induces carcinogenesis in livestock, and in animals and human cell lines. Ptaquiloside has been found in the milk of cattle, goats, and sheep that grazed on P. aquilinum in pastures. Ptaquiloside is water-soluble and washes away from the plants into the soil with rainwater. It has been found in streams and groundwater wells. The International Agency for Research on Cancer has classified bracken fern as a Group 2B carcinogen. However, P. aquilinum has long been used as a folk remedy in various regions. Several studies have identified its medicinal value and bioactive compounds with potential pharmacological activity. Pterosin B and its analogues exhibit anti-osteoarthritis, anti-Alzheimer’s disease, neuroprotective, anti-cardiomyocyte hypertrophy, anti-diabetic, and smooth muscle relaxant properties. Ptaquiloside also induces apoptosis in certain human cancer cell lines and acts as an anticancer agent. Therefore, pterosins and ptaquiloside have therapeutic properties. Other compounds, including some flavonoids and polysaccharides, act as antimicrobial, antifungal, and immunomodulatory agents. Based on their structures, it is possible to develop medicines with these therapeutic properties, particularly those containing pterosins and ptaquiloside. However, more research is needed on their use in medicinal treatments. Full article

Background/Objectives: Galleria mellonella (G. mellonella) larvae have emerged as a valuable in vivo model for antifungal drug screening. This study aimed to determine the optimal inoculum concentrations of Candida albicans (C. albicans) in G. mellonella, as well as the appropriate fluconazole concentrations, in order to standardize a preliminary screening method for compounds with antifungal activity. Methods: Larvae were infected with four C. albicans strains, including two reference strains (ATCC^® 10231 and ATCC^® 90028) and two oral isolates (A1 and A2). Fluconazole toxicity was evaluated at doses of 20, 40, and 80 mg/kg over a 72 h period. In the treatment assays, larvae were infected via the left pro-leg and treated with fluconazole, administered as a single or two doses, one hour after infection. Larval viability was monitored over five days based on movement, cocoon formation, and melanization, and survival data were analyzed using Kaplan–Meier curves and the log-rank test. Results: Fluconazole showed no toxicity at the tested concentrations. Infection with up to 2 × 10⁷ cells/mL was non-lethal for most strains, except for A2, which exhibited 50% mortality within 48 h but it was effectively controlled with a single 20 mg/kg dose of fluconazole. Infection with 2 × 10⁸ cells/mL resulted in complete mortality within 48 h; however, a single 80 mg/kg dose significantly improved survival. Conclusions: The G. mellonella model proved to be a suitable and reproducible in vivo system for the preliminary screening of antifungal compounds. The standardized experimental conditions established in this study support its applicability for evaluating antifungal activity in early research stages. Future studies should expand this approach to different fungal species and antifungal agents, as well as explore its applicability in combination therapies. Full article

Brown spot, caused by the seedborne fungus Bipolaris oryzae, remains a major constraint in rice production. Here, we used in vitro and in vivo assays to evaluate the biocontrol potential of three Bacillus strains (Ba. cereus OQ725688.1, Ba. velezensis OP938696.1, and Ba. subtilis OP937353.1) against Bi. oryzae in two rice cultivars (“Rubelita” and “Predileta”). Ba. cereus showed the highest in vitro mycelial inhibition (≈95%), whereas Ba. velezensis was the most effective under greenhouse conditions, reducing disease severity by up to 60% and increasing seedling vigor by 51% compared with infected controls. “Predileta” showed the strongest response to bacterial treatment, maintaining severity scores below 2 even under high inoculum pressure. Functional assays confirmed that all strains displayed amylolytic, catalase, and phosphate-solubilizing activities, with Ba. velezensis uniquely expressing strong cellulase and protease activities. Genome analysis of Ba. velezensis OP938696.1 revealed multiple biosynthetic gene clusters for antifungal polyketides and lipopeptides. These integrated biochemical and genomic traits demonstrate the novelty and potential of this Neotropical strain as a multifunctional agent capable of suppressing Bi. oryzae while enhancing rice seedling performance. Incorporating such a native strain into seed and soil management offers a sustainable strategy for rice protection in Neotropical systems. Full article

The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and fungal pathogen (A. solani). The binding stability and interaction dynamics of specific metabolites with fungal virulence (polygalacturonase, MAP kinase HOG1, and effector AsCEP50) and insect neuromuscular (ryanodine receptor and sodium channel protein) targets were assessed using molecular docking and 100 ns molecular dynamics simulations. Among the screened compounds, squalene and 4,7,10,13,16,19-docosahexaenoic acid, methyl ester (DHAME) exhibited the strongest binding affinities and conformational stability, with MM-GBSA binding free energies of −38.09 kcal·mol⁻¹ and −52.81 kcal·mol⁻¹ for squalene complexes in T. absoluta and A. solani, respectively. Persistent hydrophobic and mixed hydrophobic–polar contacts that stabilised active-site residues and limited protein flexibility were found by ProLIF analysis. These lively and dynamic profiles imply that DHAME and squalene may interfere with calcium signalling and stress-response pathways, which are essential for the survival and pathogenicity of pests. Hydrophobic interactions were further confirmed as the primary stabilising force by the preponderance of van der Waals and nonpolar solvation energies. The findings show that C. tora metabolites, especially squalene and DHAME, are promising environmentally friendly biopesticide candidates that have both insecticidal and antifungal properties. Their development as sustainable substitutes in integrated pest management systems are supported by their stability, binding efficacy and predicted biosafety. Full article

Background: Therapeutic drug monitoring (TDM) is essential for ensuring safe, effective, and individualized anti-infective therapy, particularly in patients with complex clinical needs. Variability in pharmacokinetics, challenges in drug administration, and high-dose regimens can compromise adherence and increase the risk of therapeutic failure or resistance. Swallowing difficulties, a common barrier to oral therapy, often necessitate alternative administration routes or customized formulations. However, interventions such as pharmaceutical compounding or manipulation of solid dosage forms may significantly alter drug bioavailability and pharmacokinetic profiles, making TDM indispensable for guiding dose adjustments and maintaining therapeutic targets. Objectives: This review not only emphasizes the clinical relevance of TDM but also addresses practical strategies that enable therapy when standard formulations are unsuitable or unavailable, while minimizing risks that could compromise treatment efficacy and safety. Special focus is given to anti-infective agents, such as antibiotics, antivirals, and antifungals, illustrating how TDM, combined with tailored pharmaceutical approaches, supports precision dosing and informed decision-making. Conclusions: Through clinical examples and pharmacokinetic considerations, we demonstrated that TDM is a cornerstone of personalized medicine, improving outcomes, and reducing adverse effects in anti-infective treatment. Full article

Background: Candida auris has emerged as a multidrug-resistant fungal pathogen, presenting significant clinical challenges worldwide. Although considerable progress has been made in antifungal research, the specific mechanisms underlying drug resistance in C. auris remain incompletely understood. To overcome this problem, natural compounds can be used as valuable alternatives. The present study aimed to evaluate the antifungal activity of NEO against C. auris and to understand the functional mechanisms underlying its antifungal activity. Methods: The antifungal activity of NEO against C. auris strain CBS10913T was examined using broth microdilution and spot assays to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Mechanistic investigations were performed using phenotypic-, biochemical-, and fluorescence-based assays to evaluate its effects on cell wall integrity, membrane permeability, efflux pump activity, oxidative stress, lipid peroxidation, biofilm formation, and host cell adherence. Hemolytic assays were performed to evaluate preliminary biocompatibility. Results: During our study, we found that NEO showed strong fungicidal activity against C. auris, with an MIC of 500 µg/mL and an MFC of 650 µg/mL, and disrupted fungal cell wall integrity, significantly reduced ergosterol content, and inhibited efflux pump activity, leading to increased accumulation of fluorescent substrates. NEO induced increased intracellular reactive oxygen species, leading to oxidative-mediated lipid peroxidation and DNA damage. Moreover, NEO also suppressed stress biofilm formation, reduced metabolic activity, and decreased adherence to buccal epithelial cells, and it showed negligible hemolytic activity up to 2× MIC, indicating preliminary biocompatibility. Conclusions: This study demonstrates that NEO utilizes broad antifungal activity through multiple functional and phenotypic mechanisms, including disruption of membrane integrity, inhibition of efflux pump, induction of oxidative stress, and suppression of biofilm formation. Although the direct effects on pathogenicity-related genes or proteins were not studied, the findings still show NEO as a promising natural antifungal agent. Full article

This study aimed to develop biofumigation strategies against chestnut fruit rot caused by Botryosphaeria dothidea. An endophytic strain, FPYF2509, was isolated from Castanea mollissima fruit and identified as Trichoderma nordicum using morphological and phylogenetic (tef1, rpb2) analyses. Antifungal volatile organic compounds (VOCs) were analyzed using headspace solid-phase microextraction and gas chromatography–mass spectrometry during dual-culture interactions with pathogens. The volatiles from the interaction exhibited to inhibit pathogen growth. Particularly an induced myrtenol, demonstrated strongly biofumigation activity in vitro, with a lowest observed effect concentration of 0.02 µL/mL, minimum inhibitory concentration and a minimum fungicidal concentration of 0.2 µL/mL against B. dothidea. In vivo, fumigation with 0.2 µL/mL myrtenol significantly reduced disease incidence from 83.3% to 17.39%, achieving a 79.1% control efficacy. This work presents endophytic T. nordicum FPYF2509 as a promising biocontrol agent and identifies myrtenol, of fungal interaction origin, as a novel and effective mycofumigant for postharvest disease management. Full article

The cyclic adamantane framework possesses unique properties such as bulkiness, symmetry, and high lipophilicity. Research aimed at discovering new pharmaceutical agents within the adamantane series continues. In the present work, a targeted modification was carried out to combine two pharmacophore fragments—adamantane and piperidine—within a single molecule. Based on a series of N-substituted piperidin-4-ones, the corresponding secondary alcohols were obtained by reduction with sodium borohydride in isopropanol and subsequent acylation of these alcohols with adamantane carbonyl chloride yielded the corresponding adamantane-carboxylate esters. The structure of the synthesized compounds was studied by NMR methods, including COSY (¹H-¹H), HMQC (¹H-¹³C) and HMBC (¹H-¹³C) techniques. The values of chemical shifts, multiplicities, and integrated intensities of ¹H and ¹³C signals in one-dimensional NMR spectra were determined. The results of COSY (¹H-¹H), HMQC (¹H-¹³C), and HMBC (¹H-¹³C) revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The cytotoxic activities of the synthesized compounds were studied. It was found that the synthesized substituted piperidines bearing an adamantane fragment exhibit in vitro antimicrobial and antifungal activity against museum microbial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538-P, Candida albicans ATCC 10231, Cryptococcus neoformans) and demonstrate significant advantages over the reference drugs used in clinical practice, such as fluconazole and ampicillin. These compounds are therefore recommended for further in-depth studies. Full article

Imidazole is, from a structural point of view, a heterocycle consisting of three C atoms and two N atoms, belonging to the class of diazoles, having two N atoms at the first and third positions in the aromatic ring. Being a polar and ionizable aromatic compound, it has the role of improving the pharmacological properties of lead molecules, thus being used to optimize their solubility and bioavailability. Imidazole is a constituent of many important biological compounds, like histidine, histamine, and purine compounds, the most widespread heterocyclic compound in nature. In current practice, substituted imidazole derivatives play a major role in antifungal, antibacterial, anti-inflammatory, CNS active compounds, antiprotozoal, as well as anticancer therapy. Thus, imidazole derivatives have demonstrated significant anticancer activities by inhibiting the key metabolic pathways essential for tumor cell growth and survival. Nitroimidazoles, for instance, have been employed as hypoxia-directed therapeutic agents, targeting oxygen-deprived tumor tissues, while mercaptopurine derivatives are well-established in oncological treatments. Structural modifications of the imidazole nucleus have led to the novel compounds exhibiting increased selective cytotoxicity against cancer cells, while sparing normal healthy cells. In accordance with what has been stated, this review highlights recent research on the medicinal and pharmaceutical interest of novel imidazole derivatives, emphasizing their potential in the development of new drugs. Full article

The rising incidence of invasive fungal infections (IFIs) and the associated antifungal resistance underscore the need for antifungal stewardship (AFS) programs. Evaluating physicians’ knowledge and practices is crucial for identifying gaps and planning effective AFS interventions. A self-administered questionnaire was distributed to staff and resident physicians at a referral university-affiliated hospital in Greece in November 2025. The survey examined participants’ knowledge on fungal diagnosis and treatment, their prescribing attitudes and practices, and their AFS-related education, knowledge and preferences. In total, 70 physicians (46 residents and 24 staff consultants) participated in the survey from medical departments (63%), surgical departments (30%), and intensive care units (7%). Physicians surveyed demonstrated a low average knowledge score of 36.6% correct answers (SD, 22.7%; range 0% to 90%) regarding IFIs and antifungal agents, and significant variation was observed across different hospital departments. Awareness of risk factors for IFI varied widely, with recognition rates of different factors ranging from 10% to 100% across departments. Many physicians (71%) reported a lack of confidence in prescribing antifungal therapy and reliance on infectious disease experts was common (84%). Most preferred training methods were case-based discussions and printed guidelines. The substantial knowledge gaps and low confidence in prescribing antifungals among physicians highlight the urgent need for education and implementation of local guidelines to optimize antifungal use that might improve patient outcomes. Full article

Among Candida species, several are major opportunistic fungal pathogens capable of causing a wide spectrum of infections, ranging from superficial mucosal conditions to severe systemic diseases. Their success as human pathogens is largely due to their ability to rapidly adapt to diverse host environments and develop resistance to antifungal agents. Experimental evolution provides a powerful framework for understanding these adaptive processes by observing evolutionary change in real-time. Although most studies rely on in vitro systems and a limited set of Candida species, there is strong evidence that genome plasticity, including aneuploidy, loss of heterozygosity, and copy number variation, plays a central role in driving rapid adaptation. Experimental evolution has also been applied to study the dynamics of antifungal resistance, particularly to azoles, although relatively fewer studies have explored resistance to echinocandins and polyenes. This review summarizes current knowledge on experimental evolution in pathogenic Candida species, with a focus on genome plasticity, adaptation to host-imposed stress, and particularly on the emergence of antifungal resistance. It also identifies critical research gaps, including the need for broader species coverage, investigation of underexplored antifungal classes, and evaluation of combined therapies. A deeper understanding of these dynamics is essential to improve antifungal strategies and counter the growing threat of drug-resistant Candida spp. infections. Full article

Cancer remains a significant global health burden despite advances in diagnosis and treatment. In recent years, drug repurposing has emerged as a promising strategy in oncology, offering reduced costs and shorter development timelines compared with de novo drug discovery. Among repurposed agents, the antifungal drug itraconazole has demonstrated anticancer activity across multiple tumor types, particularly when used in combination with other therapeutic modalities. In this review, we summarize current preclinical and clinical evidence supporting the use of itraconazole in cancer therapy, with a specific focus on its combination with chemotherapeutic agents and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. We highlight proposed mechanisms underlying this synergy, including modulation of tumor metabolism, angiogenesis, and immune signaling pathways. Additionally, we discuss key challenges and limitations, such as drug–drug interactions and toxicity considerations, that must be addressed to optimize clinical translation. Overall, the combination of itraconazole with chemotherapy or anti-PD-1 therapy represents a promising therapeutic strategy warranting further investigation in well-designed trials. Full article

Squalene, a hydrocarbon with several industrial applications, is obtained from plants, animals, and microorganisms. Oleaginous thraustochytrids are also potential sources of squalene. In eukaryotes, squalene, an intermediary in the sterol/cholesterol pathway, accumulates when the activity of squalene epoxidase or an Alternative SQualene Epoxidase (AltSQE) is inhibited. The objective of this study was to evaluate the polyphenols extracted from barley bagasse for enhancement of the squalene content in Thraustochytrium sp. RT2316-16. In the media supplemented with terbinafine, an antifungal compound known as an inhibitor of squalene epoxidase, or the polyphenols from barley bagasse 72 h after inoculation, the squalene concentration was 308.7 ± 0.8 and 286.5 ± 0.1 mg L⁻¹ after 168 h, respectively, whereas in the control medium, it was 85.6 ± 0.2 mg L⁻¹. The final concentrations of the lipid-free biomass (4.5 ± 0.1 g L⁻¹) and total lipids (2.5 ± 0.3 g L⁻¹) were not affected by the polyphenols from barley bagasse; on the contrary, the concentration of total lipids in the terbinafine treatment was 30% lower than in the control. In RT2316-16, the gene coding for AltSQE, which is not found in all thraustochytrids, was upregulated under the control treatment, whereas its relative expression was not affected by terbinafine. The squalene accumulation in RT2316-16 in response to the treatment with polyphenols and the antifungal agent makes this strain a promising source of the triterpenoid. Full article

Candida spp. are important opportunistic human fungal pathogens. This study aimed to identify and characterize Candida spp. obtained from patients admitted to an Intensive Care Unit (ICU), focusing on virulence attributes and susceptibility to antifungal agents. A total of 131 isolates from oral and tracheobronchial secretions of adult ICU patients were evaluated. Phenotypic identification was performed using chromogenic culture media for Candida, followed by MALDI-TOF mass spectrometry, with representative isolates confirmed by ITS sequencing. Antifungal susceptibility to fluconazole, ketoconazole, and amphotericin B was determined only by the agar disk diffusion method, and virulence was assessed through esterase, DNase, protease, and hemolytic activity assays. C. albicans was the prevalent species, followed by C. tropicalis, C. krusei, C. glabrata, C. parapsilosis, C. dubliniensis, C. lusitaniae, and C. guilliermondii. Antifungal resistance rates reached 51.1% for fluconazole, 42.7% for ketoconazole, and 19.1% for amphotericin B, as determined by disk diffusion method. Overall, 64.9% of the isolates exhibited esterase activity, 18.3% DNase, 45.8% protease, and 67.2% exhibited hemolytic activity. Oral isolates were more frequent than tracheal isolates and demonstrated a higher prevalence of antifungal resistance and virulence traits. These findings underscore the epidemiological importance of characterizing Candida species in hospitals to better understand the yeast profile and to support adequate clinical management. Full article

Background: Heterocyclic compounds are particularly important in medicinal chemistry. With a range of therapeutic uses, benzimidazoles and quinolines are both key heterocycles in medicinal chemistry. A number of hybrid heterocyclic compounds have been reported in recent years because they typically have better therapeutic properties than single heterocyclic rings. Methods: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including “benzimidazole”, “quinoline”, “benzimidazole-quinoline hybrids”, “antibacterial”, “antifungal”, “antimalarial” and “hybrid complexes”. Results: This review summarizes the synthetic methodologies for benzimidazole–quinoline hybrids, benzimidazole– quinolinones, and benzimidazole–quinoline metal complexes, along with their antimicrobial and antimalarial activities and the reported structure–activity relationship (SAR) studies. The importance of halogen substitution, particularly with chlorine and fluorine atoms, as well as the structure of the linker between the benzimidazole and quinoline rings—specifically chain length, the presence of oxygen, sulfur, or nitrogen atoms, and heterocyclic moieties—is highlighted. A series of benzimidazole–quinoline hybrids exhibit antimalarial and antitrypanosomal activities or show enhanced antimicrobial properties due to the incorporation of a five-membered heterocycle in addition to the two existing heterocyclic rings. Notably, several hybrids from different compound series exhibit very low minimum inhibitory concentrations (MICs) in the range of 1–8 µg/mL, along with low cytotoxicity, supporting their potential for further investigation as antimicrobial agents. Conclusions: This review summarizes the synthetic methods, medicinal properties, and structure–activity relationship (SAR) studies of benzimidazole–quinoline hybrids reported between 2002 and 2026. Full article