Search Results (2,214)

Background/Objectives: This study aimed to synthesize a novel, high-molecular-weight acyclic heterocyclic compound, compound 5, via a one-pot reaction between Trichloroisocyanuric acid (TCCA) and ethanolamine, and evaluate its anticancer, antioxidant, and antifungal activities. Methods: Its complex tetrameric structure, assembled through N-N linkages, was unequivocally confirmed by a full suite of spectroscopic techniques including IR, ¹H & ¹³C NMR, ²D-NMR, and high-resolution mass spectrometry (LC/Q-TOF/MS). The MTT assay was used to assess the anticancer activity of compound 5 against four different human cancer cell lines. Results: The findings indicate that human colon (HT29) and ovarian (OVCAR3) cancer cells were sensitive to the treatment, whereas brain (glioblastoma) (T98G) cancer cells were resistant. The most pronounced cytotoxic effect was observed in pancreatic (MiaPaCa2) cancer cells. Notably, compound 5 exhibited potent antifungal properties, achieving 100% inhibition of the pathogenic water mould Saprolegnia parasitica zoospores at 100 µM after 10 min. Molecular docking studies corroborated the biological data, revealing a high binding affinity for key cancer and fungal targets (Thymidylate Synthase and CYP51), providing a strong mechanistic basis for its observed activities. Conclusions: These findings establish compound 5 as a promising dual-action agent with significant potential as both a targeted anticancer lead and an eco-friendly antifungal for applications in aquaculture. Full article

Coccidioides immitis and Coccidioides posadasii, the causative agents of coccidioidomycosis, represent a major public health concern in endemic regions of North and South America. The disease spectrum ranges from mild respiratory illness to severe disseminated infections, with thousands of cases reported annually in the United States and an increasing recognition of its global impact. Despite existing antifungal therapies, treatment remains challenging due to toxicity, drug resistance, and limited therapeutic options. High-throughput screening platforms have revolutionized drug discovery for infectious diseases; however, progress in antifungal screening for Coccidioides spp. has been hampered by the requirement for Biosafety Level 3 (BSL-3) containment. To overcome these barriers, we leveraged an attenuated C. posadasii strain that can be safely handled under BSL-2 conditions. Here, we describe the development and optimization of 96-well and 384-well plate screening methodologies, providing a safer and more efficient platform for antifungal discovery. This approach enhances the feasibility of large-scale screening efforts and may facilitate the identification of novel therapeutics for coccidioidomycosis. Full article

Invasive aspergillosis is an opportunistic infection caused by the Aspergillus species. It is a significant cause of morbidity and mortality in susceptible populations, including recipients of bone marrow and solid organ transplants. Azole antifungals have remained the first-line treatment for invasive aspergillosis for a long time; however, the advance of azole resistance in Aspergillus fumigatus, driven predominantly by extensive commercial and agricultural use of azole fungicides and environmental exposure of susceptible populations to the resistant strains, renders the traditional therapeutic approaches less effective and results in further increase in mortality. The epidemiology, molecular mechanisms of azole resistance, diagnostic approaches, and clinical implications of azole resistance in Aspergillus fumigatus sensu stricto will be discussed in this article (for ease of comprehension, the rest of this article will refer to A. fumigatus sensu stricto as A. fumigatus). Full article

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

To explore superior biocontrol resources for Rhododendron brown spot disease, five antagonistic fungal strains exhibiting significant inhibitory activity against the pathogen responsible for RBS were isolated from healthy Rhododendron hybridum Ker Gawl leaves. Among them, strain DJW5-2-1 demonstrated the highest inhibition rate, reaching 63.88% against the pathogenic fungus. Based on morphological characteristics and multigene phylogenetic analysis (ITS, β-tubulin, and tef1-α), DJW5-2-1 was identified as Diaporthe phoenicicola (Traverso & Spessa) Udayanga, Crous & K.D. Hyde. Dual culture assays further confirmed its broad-spectrum antifungal activity, with inhibition rates ranging from 39.15% to 72.54% against various phytopathogenic fungi. Biochemical analyses revealed that DJW5-2-1 secretes multiple extracellular enzymes and exhibits plant growth-promoting traits. In both in vitro and potted plant efficacy assays, the biocontrol efficacy of strain DJW5-2-1 against RBS was 49.67% and 50.61%, respectively, indicating that strain DJW5-2-1 exhibits a certain level of control efficacy against RBS. Through pot experiments, we found that strain DJW5-2-1 could promote the growth of rhododendron seedlings and significantly increase growth indicators. Among these indicators, the growth-promoting rates of plant height and stem diameter were 15.27% and 41.27%, respectively. Moreover, DJW5-2-1 contributed to improved host resistance by elevating the activities of key defense-related enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Taken together, these findings suggest that strain DJW5-2-1 represents a promising microbial agent for the integrated control of RBS and the development of fungal-based biofertilizers. Further investigation is warranted to assess its performance under field conditions and elucidate its underlying mechanisms of action. Full article

Tomato (Solanum lycopersicum L.) is among the most economically significant and nutritionally valuable vegetable crops grown globally. However, fungal diseases such as Early Blight caused by Alternaria alternata are a major factor limiting yield and fruit quality in tomato production. This study investigates the biocontrol potential of locally isolated rhizobacterium Pseudomonas yamanorum against A. alternata, the causal agent of early blight in tomato, under both in vitro and in planta conditions. In vitro assays demonstrated significant antifungal activity; in the dual confrontation assay, P. yamanorum (10⁸ CFU/mL) reduced A. alternata mycelial growth by 68.7%, while spore germination was inhibited by 88.7%. In planta trials demonstrated that plants treated with P. yamanorum (10⁷ CFU/mL) alone exhibited the lowest disease severity (2.5). The treatments also significantly enhanced plant growth, with shoot length reaching 45 cm versus 26 cm in infected controls. Biochemical analyses revealed increased catalase (94.84 units mg⁻¹ protein min⁻¹), peroxidase (5.83), and ascorbate peroxidase (67.01) activities in treated plants. Total polyphenol and protein contents also increased (0.81 mg/g and 15.82 mg/g, respectively). Furthermore, P. yamanorum treatments maintained fruit quality parameters such as firmness (3.13), sugar content (6.43 °Brix), and juice yield (55.88%), while reducing malondialdehyde (2.02 µmol/g Dry Weight) and electrical conductivity (0.59 mS/cm). These findings highlight P. yamanorum as a promising biocontrol agent and plant growth-promoting bacteria that improve disease resistance, which can be combined with salicylic acid to further enhance crop vigor and fruit quality under biotic stress. Full article

Background: Seborrheic dermatitis (SD) is a chronic, recurrent inflammatory dermatosis that primarily affects seborrheic areas such as the scalp, face, and upper trunk. Its etiology is multifactorial, involving sebaceous gland activity, immune dysregulation, skin barrier dysfunction, and alterations in the microbiome, particularly an overgrowth of Malassezia spp. Objective: This review provides an updated overview of the pathophysiological mechanisms of seborrheic dermatitis and critically examines current therapies and emerging treatments. Methods: A narrative review of the recent literature was conducted, including preclinical studies, clinical trials, and real-world evidence regarding SD pathogenesis and therapy. Special attention was paid to molecular pathways, microbiome-modulating strategies, and novel therapeutic agents. Results: Advances in transcriptomic and microbiome profiling have revealed a complex immunoinflammatory environment in SD, involving predominantly Th1, Th17, and Th22 axes. Conventional therapies are mainly based on antifungals, topical corticosteroids, and calcineurin inhibitors. However, new therapeutic approaches are under investigation, including PDE4 inhibitors (roflumilast, crisaborole, and apremilast), topical and oral JAK inhibitors, probiotics, and microbiome-targeted therapies. These agents offer promising results in selected patients, particularly those with refractory disease or facial involvement. Conclusions: SD remains a challenging condition due to its relapsing course and limited long-term therapeutic options. Emerging therapies represent a valuable opportunity to address unmet clinical needs, particularly in patients with severe, recurrent, or treatment-resistant forms. Full article

The emergence of Candida auris as a disheartening fungal pathogen in healthcare settings has prompted urgent re-evaluation of containment and mitigation strategies. This review critically examines the biological persistence, environmental adaptability, and resistance to standard antifungal therapies of the pathogen, particularly regions with limited surveillance infrastructure. Based on regional experiences, such as those in Saudi Arabia and the Middle East in general, the study reveals systemic weaknesses in diagnosis, reporting, and environmental sanitation. Special consideration is paid to the combination of new disinfection technologies, including ultraviolet irradiation systems and hydrogen peroxide vaporisation, with institutional behaviour change strategies. This discussion shows the importance of synchronising technological development with frequent employee contributions and cross-functional planning. It also encourages the international standardisation of diagnostic platforms and the launch of real-time genomic surveillance to reveal evolutionary trends. Finally, the findings justify the shift towards proactive models of infection control that are founded on the resilience of systems and the agility of institutions. This paper is a synthesis of epidemiological patterns, decontamination strategies and behavioural knowledge to contribute to an emerging body of knowledge that can help to fortify healthcare settings against current fungal threats. Full article

Larch shoot blight, caused by Neofusicoccum laricinum, threatens global larch resources, while conventional chemical control is constrained by pollution and resistance. To address this gap, we integrated metabolomics, transcriptomics, and antifungal efficacy assays to identify Fraxetin, a disease-induced phytoalexin, and to elucidate its antifungal activity and mechanism. Metabolomics showed infection-triggered accumulation of Fraxetin in resistant Larix olgensis shoots. Antifungal experiments showed that within the range of 68–1088 μg/mL, the optimal antifungal concentration was 1088 μg/mL. When inoculated larches were treated with 1088 μg/mL Fraxetin, the maximum inhibition rate of pathogen growth reached 66.67% within 12 days, and the symptoms of the treated plants were alleviated. Transcriptomics revealed activation of damage responses, disruption of oxidative homeostasis, and compromised membrane integrity in the pathogen under Fraxetin treatment. Physiological measurements confirmed increased lipid peroxidation, redox collapse, membrane leakage, and reduced fungal viability. These findings indicate a lipid peroxidation–mediated oxidative–membrane mode of action and support the potential of plant-derived Fraxetin for more sustainable management of larch shoot blight. Full article

Background: Candida auris has emerged as a significant public health threat causing life-threatening systemic infections. Of particular concern is the frequency of multidrug resistance, high transmissibility, and persistence in the environment; thus, there is a need for novel strategies to prevent and treat this infection. We previously generated a “pan-fungal” vaccine candidate, NXT-2, which induces protective immunity against several invasive fungal infections. Methods: In this study, we investigated the efficacy of NXT-2 immunization against systemic C. auris infection in an immunosuppressed murine model and investigated the possible mechanisms by which NXT-2 protection is mediated in vitro. Results: Active immunization afforded significant improvement in survival and reduced morbidity in neutropenic mice challenged intravenously with C. auris compared to controls (48.4% vs. 13.8%). To assess humoral immunity in promoting protection, passive immunization with NXT-2-specific IgG to neutropenic mice prior to the challenge with C. auris resulted in significantly higher survival (42% vs. 0%) and low morbidity compared to controls. Sera from NXT-2-immunized animals inhibited biofilm formation and enhanced opsonophagocytic killing of multiple C. auris clades in vitro. Conclusions: These findings show that immunization with NXT-2 improves survival in C. auris infection and that NXT-2 antibodies promote antifungal activity in vitro and in vivo. These results extend the range of the pan-fungal NXT-2 vaccine to include protection against systemic C. auris-mediated infection and provide a rationale for the development of NXT-2 monoclonal antibodies for the treatment of C. auris infections. Full article

Background/Objectives: Invasive pulmonary aspergillosis (IPA) represents a critical respiratory condition mainly caused by Aspergillus fumigatus and other ubiquitous species such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. IPA clinical management has been complicated by diagnostic challenges and therapeutic difficulties due to antifungal intrinsic or secondary resistance episodes. Despite this assumption, few scientific data have been reported about possible antifungal drug combinations. Herein, we propose an experimental evaluation using isavuconazole/amphotericin B and isavuconazole/caspofungin in vitro synergy assays to investigate their combined activity on Aspergillus spp. IPA clinical isolates. Methods: We globally analyzed 55 Aspergillus spp. isolates, practicing the gradient test methods with single and combined antifungal drugs through the MIC Strip test (Liofilchem, Roseto degli Abruzzi, Italy). The collected MIC values were interpreted according to the EUCAST guidelines and classified as synergy, additivity, indifference, and antagonism cases through a FIC index calculation. A statistical analysis on species’ correlation with particular synergy testing results was finally provided. Results: Despite an interesting activity against A. fumigatus, isavuconazole/amphotericin B did not report statistical significance, obtaining a consistent antagonism percentage (43.6%). On the other hand, isavuconazole/caspofungin showed a promising in vitro synergic activity, except for A. flavus isolates. Conclusions: Synergy testing demonstrated a significant species-specific trend. Future studies should be focused on Aspergillus spp. isolates and antifungal in vitro synergy testing, aiming to discourage or recommend any specific antifungal combinations, depending on the isolated species. Full article

Coumarin derivatives, whether natural or synthetic, have attracted considerable interest from medicinal chemists due to their versatile biological properties. Their appealing pharmacological activities—such as anticancer, anti-inflammatory, neuroprotective, anticoagulant, and antioxidant effects—combined with the ease of their synthesis and the ability to introduce chemical modifications at multiple positions have made them a widely explored class of compounds. In the scientific literature, there are many examples. On the other hand, dithiocarbamates, originally employed as pesticides and fungicides in agriculture, have recently emerged as potential therapeutic agents for the treatment of serious diseases such as cancer and microbial infections. Moreover, dithiocarbamates bearing diverse organic functionalities have demonstrated significant antifungal properties against resistant phytopathogenic fungi, presenting a promising approach to combat the growing global issue of fungal resistance. Dithiocarbamates linked to coumarin derivatives have been shown to exhibit cytotoxic activity against various human cancer cell lines, including MGC-803 (gastric), MCF-7 (breast), PC-3 (prostate), EC-109 (esophageal), H460 (non-small cell lung), HCCLM-7 (hepatocellular carcinoma), HeLa (cervical carcinoma), MDA-MB-435S (mammary adenocarcinoma), SW480 (colon carcinoma), and Hep-2 (laryngeal carcinoma). Numerous studies have revealed that the inclusion of a dithiocarbamate moiety can provide central nervous system (CNS) activity, particularly through inhibitory potency and selectivity toward acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). Recently, it has been reported that coumarin–dithiocarbamate derivatives exhibit α-glucosidase inhibitory effects and also possess promising antimicrobial activity. This study presents an overview of recent progress in the chemistry of coumarin–dithiocarbamate derivatives, with a focus on their biological activity. Previous review papers focused on coumarin derivatives as multitarget compounds for neurodegenerative diseases and described various types of compounds, with dithiocarbamate derivatives representing only a small part of them. Our work deals exclusively with coumarin dithiocarbamates and their biological activity. Full article

Candida auris has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of C. auris candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in ERG11, E709D in CDR1, A583S in TAC1b, K52N and E1464K in SNQ2, K74E in CIS2, M192I in ERG4, a novel mutation S237T in CRZ1, and variants in GCN5, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in C. auris. These findings underscore the need for further research to understand C. auris resistance pathways and to guide effective clinical management strategies. Full article

The increasing prevalence of antimicrobial resistance and the persistent challenge of infectious diseases highlight the critical necessity for novel approaches that integrate pathogen management with swift detection methods. Carbon dots (CDs) are a versatile class of fluorescent nanomaterials that have garnered increasing attention owing to their tunable surface chemistry, strong photoluminescence, high stability, and biocompatibility. Recent studies demonstrate that CDs possess broad-spectrum antibacterial and antifungal activities via multiple mechanisms, including the generation of reactive oxygen species, disruption of membranes, inhibition of biofilms, and synergistic interactions with conventional antimicrobials. The performance is significantly affected by precursor selection, heteroatom doping, and surface functionalization, with minimum inhibitory concentrations reported to range from highly potent at the microgram level to moderate at elevated concentrations. The intrinsic fluorescence of CDs, in addition to their antimicrobial activity, facilitates their use as sensitive and selective probes for microbial detection, allowing for rapid and real-time monitoring in biomedical, food safety, and environmental settings. This review summarizes recent advancements in the antimicrobial properties of carbon dots (CDs) and their fluorescence-based applications in microbial detection. It emphasizes their theranostic potential and future prospects as multifunctional nanomaterials for combating infectious diseases and ensuring microbial safety. Full article

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article