Search Results (748)

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora infestans, Botrytis cinerea, and Fusarium oxysporum. Compound 3b exhibited exceptional antifungal activity against R. solani, with an EC₅₀ of 2.10 mg/L. Moreover, it substantially inhibited sclerotia germination (81.5% at 9 mg/L) and formation (79.3% at 9 mg/L), surpassing octhilinone. The protective effect on detached rice leaves and rice seedlings was found to be 43.4% and 85.2% at 100 mg/L, respectively, and 64.4% and 89.4% at 200 mg/L. These findings suggest that benzothiazole and benzoxazole selenones represent promising lead compounds for sustainable plant disease management. Full article

Aspergillus fumigatus, a saprophytic fungus, causes aspergillosis, primarily affecting the immunocompromised. The efficacy of triazole antifungals is compromised by resistance that has developed both clinically and environmentally. Widespread agricultural use of similar triazole fungicides selects for resistant genotypes, leading to potential food contamination and compromising treatment. This study assessed the presence of azole-resistant A. fumigatus in minimally processed food items commonly consumed in Brazil. A total of 25 commercial samples, including black pepper, yerba mate, and green coffee beans, were collected from different regions. Forty-two A. fumigatus isolates were recovered and screened for susceptibility to agricultural and clinical triazoles by determining EC₅₀ values for tebuconazole (0.04–0.7 µg/mL), itraconazole (0.06–0.5 µg/mL), and voriconazole (0.07–0.15 µg/mL). Sequence analysis of the CYP51A gene revealed the presence of M172V mutation, none of which are associated with resistance. Microsatellite genotyping indicated high genotypic diversity and genetic relatedness among isolates from different food sources. Although no azole-resistant phenotypes were identified, the consistent recovery of A. fumigatus from products not directly exposed to azole fungicides highlights the need for continued surveillance. Agricultural environments remain critical hotspots for the emergence and dissemination of resistance, reinforcing the importance of integrated One Health strategies in antifungal resistance monitoring. Full article

Subcutaneous mycoses are a heterogeneous group of chronic fungal infections, usually acquired through traumatic inoculation of environmental fungi and particularly severe in immunocompromised and critically ill patients. These infections involve pathogens with marked morphological and physiopathological diversity, resulting in significant diagnostic and therapeutic challenges. Conventional treatment relies on systemic antifungals such as amphotericin B, itraconazole, and other azoles; however, these therapies are often limited by poor tissue penetration, adverse effects, and prolonged treatment regimens, especially in vulnerable patient populations. In this context, nanodrugs have emerged as promising alternatives by improving solubility, stability, bioavailability, and targeted delivery to infection sites. This review conducted a comprehensive literature search in PubMed, SciELO, ScienceDirect, Web of Science, and Scopus, identifying 31 eligible studies that developed and evaluated antifungal nanosystems using in vitro, ex vivo, and/or in vivo models. Quantitative outcomes included minimum inhibitory concentration (MIC), colony-forming units (CFU), inhibition halo diameter, and survival assays. Overall, the evidence indicates that several nanosystems may overcome key pharmacological limitations of conventional antifungals and enhance therapeutic outcomes. Nevertheless, important translational challenges remain, including toxicity, long-term safety, scalability, and regulatory approval, which must be addressed before clinical implementation. Full article

The rising global incidence of Candida parapsilosis infections is increasingly complicated by antifungal resistance, resulting in frequent therapeutic failure. This study investigated the potential of the natural compound catechin to enhance the efficacy of fluconazole through synergistic interaction. We evaluated the susceptibility of C. parapsilosis clinical isolates and a reference strain to combinations of catechin and fluconazole using standardized microbiological assays and molecular techniques. In vivo efficacy was assessed using the Galleria mellonella infection model. Mechanistic studies included the measurement of intracellular reactive oxygen species (ROS) production and plasma membrane permeability. Catechin alone caused growth retardation in all strains. However, the combination of catechin and fluconazole resulted in complete growth inhibition of the reference strain and significant growth reduction in azole-resistant clinical isolates. While the combination slightly increased intracellular ROS production, no significant changes in plasma membrane permeability or membrane potential were observed. Notably, catechin induced the expression of the resistance-associated genes CpTAC1 and CpCDR1B in resistant isolates. In vivo experiments demonstrated that catechin significantly reduced mortality in G. mellonella larvae infected with C. parapsilosis. These findings suggest that catechin is a promising candidate for developing synergistic antifungal therapies against resistant Candida species. Full article

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, corticosteroids, and renal replacement therapy. Six days after discharge, she was readmitted with fever, leukopenia, thrombocytopenia, cavitary lung lesions, and multiple erythematous nodules on the limbs and mammary regions. Bronchial aspirate cultures detected K. pneumoniae, while progressive cutaneous lesions required surgical debridement. Histopathology revealed angioinvasive septate hyphae, and MALDI-TOF identified A. flavus. The K. pneumoniae strain was extensively drug resistant; A. flavus was susceptible only to azoles. Despite targeted therapy, lesions progressed requiring bilateral mastectomy. Conclusions: This case illustrates a previously unreported scenario in which secondary immunosuppression after severe sepsis led to concurrent cutaneous A. flavus infection and extensively drug-resistant (XDR) K. pneumoniae. Early recognition of mixed fungal–bacterial infections is essential for appropriate management. Full article

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

This study evaluated the in vitro interaction of 5-fluorouridine (5-FUrd) with antifungal drugs and examined the role of efflux pumps in 5-FUrd resistance. Eleven reference Candida strains and twenty-three clinical C. albicans isolates from gynecological patients were tested. The antifungal activity of 5-FUrd alone and in combination with amphotericin B, fluconazole, voriconazole, caspofungin, and flucytosine was assessed using the checkerboard microdilution method. Efflux pump activity was evaluated using two inhibitors: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and verapamil. 5-FUrd exhibited antifungal activity against both the reference and clinical Candida strains, with MIC values ranging from 0.1 µg/mL to 409.6 µg/mL. The checkerboard assays revealed primarily no interactions in the reference Candida strains, whereas the reference C. albicans and clinical C. albicans isolates showed notable synergy between 5-FUrd and fluconazole, voriconazole, or caspofungin. The efflux pump inhibitors reduced the MICs of 5-FUrd in the resistant strains of C. lusitaniae, C. kefyr, and particularly C. krusei, suggesting efflux-mediated resistance mechanisms. This study highlights the potential of 5-FUrd, alone or combined with azoles or caspofungin, as an adjunct therapy against Candida infections. It also suggests that reduced susceptibility may be linked to efflux pump activity in certain strains. Full article

In the context of evolving antifungal resistance and increasing reports of clinical outbreaks of non-albicans Candida spp. invasive infections, the rapid detection of resistant patterns is of the utmost importance. Currently, an azole-resistant Candida parapsilosis clinical outbreak is ongoing at Pisa University Hospital. Resistant isolates bear both Y132F and S862C amino acid substitutions. Based on the data and isolates retrieved during the clinical outbreak, mass spectrometry was used to investigate the differences between fluconazole-resistant and -susceptible clinical strains directly from yeast colonies isolated from agar culture media. A total of 39 isolates, 16 susceptible and 23 resistant, were included. Spectra were processed following a standardized pipeline. Several supervised machine learning classifiers such as Random Forest, Light Gradient Boosting Machine, and Support Vector Machine, with and without principal component analysis were implemented to discriminate resistant from susceptible isolates. Support Vector Machine with principal component analysis showed the highest sensitivity in detecting fluconazole resistance (100%). Despite these promising results, external prospective validation of the algorithm with a higher number of clinical isolates retrieved from multiple clinical centers is required. Full article

Coccidioides immitis and C. posadasii are the causative agents of coccidioidomycosis (CM) or Valley Fever, endemic to the alkaline deserts of North and South America. Clinical treatment of CM is predominantly limited to the triazole and polyene drug classes. There are limited therapeutic options for the treatment of CM, most commonly requiring prolonged courses of therapy with established antifungal agents such as azoles and Amphotericin B, which often lead to toxicity and drug resistance. Clearly, there is a need to develop novel and better antifungal drugs against CM. This review examines both repurposed and recently discovered compounds in various stages of development for the treatment of CM. Full article

Leishmaniasis, a neglected tropical disease caused by protozoa of the genus Leishmania, presents a wide clinical spectrum from self-healing cutaneous lesions to life-threatening visceral disease. Its epidemiology and severity vary by geography and species (Old vs. New World), vector biology, and host factors. Pathogenesis reflects a tripartite interplay among parasite, host, and sand fly saliva. Parasite virulence determinants—including lipophosphoglycan, GP63, proteophosphoglycans, and GPI-anchored antigens—facilitate complement evasion, macrophage entry, and suppression of microbicidal pathways. Innate defenses (complement, neutrophils, dendritic cells, NK cells) and PRR signaling (TLRs/NLRs) shape early outcomes, while the balance between Th1-mediated macrophage activation and Th2/regulatory responses dictates clearance versus persistence. Clinically, most infections remain cutaneous; a minority disseminate to mucosa, driven by immunopathology and species traits. Management must be individualized by Leishmania species, lesion burden/site, immune status, geographic region and drug availability. Local therapies (intralesional antimonials, cryo-/thermotherapy) are suitable for limited disease, whereas systemic agents (antimonials, amphotericin B, miltefosine, pentamidine, azoles) are reserved for complex, mucosal, disseminated, or immunosuppressed cases. Drug resistance—via altered uptake/efflux, metabolic rewiring, and genomic plasticity—increased toxicity and treatment failure. Targeting parasite virulence and unique metabolic pathways, improving species-specific diagnostics, and integrating host-directed strategies are priorities to shorten therapy and improve clinical outcomes. Full article

Azole compounds are extensively utilized in plant protection products for managing pests and diseases in both agriculture and horticulture. Moreover, azoles are the most extensively used class of fungicides worldwide. In addition to being effective against human pathogenic fungi, they are used in the food and agricultural industries to prevent and control fungal infections in crops. Unfortunately, the extensive use of azoles and subsequent overexposure have led to undesirable effects on ecosystems and non-target aquatic and terrestrial organisms. In the last decade alone, the European Union (EU) has prohibited numerous pesticides, many of which are based on azoles. Numerous azoles, especially triazoles, pyrazoles, imidazoles, and oxazoles, are still approved as active ingredients in plant protection products in the EU due to their excellent activity and minimal environmental and health impacts. However, for some, the expiry date is as close as March 2026. A computational approach for estimating their effectiveness against harmful and non-target organisms in soil, as well as detailed research into the molecular mechanism of action, is used for further evaluation of the compounds. This review provides an overview of azole pesticides and a summary of recent knowledge addressing their toxicity, future prospects, methods, and strategies to overcome their limitations. Full article

Amphotericin: B (AmpB)-resistant Candida (C.) species, such as C. parapsilosis, are among the most common causes of invasive fungal infections, posing significant challenges in hospital settings. Although AmpB is considered the first-line treatment owing to its broad-spectrum fungicidal activity, its use is hampered by severe side effects and the emergence of acquired resistance, particularly in C. parapsilosis, which exhibits reduced susceptibility to polyene, azole, and echinocandin-based antifungal drugs. Here, we present findings on photodynamic therapy (PDT) that targets the opportunistic fungal pathogens C. parapsilosis and C. albicans via the use of photosensitizers from the iodocyanine and newly developed iodinated Methylene blue families. These compounds contain heavy iodine atoms that increase the production of reactive oxygen species (ROS), the agents responsible for oxidative cellular damage, via the heavy-atom effect, which promotes intersystem crossing (ISC) and triplet-state formation. A strong antifungal effect was observed against AmpB-resistant C. parapsilosis, indicating a correlation between the quantum yield of ROS generation and the photosensitizing efficacy under near-infrared (NIR) light irradiation. The combination of efficient cellular uptake and enhanced ROS generation positions iodinated photosensitizers as promising candidates for the treatment of drug-resistant Candida strains. Full article

This study evaluates the abatement of four common azole fungicides—prochloraz, tebuconazole, tetraconazole, and penconazole—using ozonation (O₃), electro-oxidation (EO on boron-doped diamond anode), and their coupling (EO–O₃). A central composite design (CCD) with three coded factors—current (A), electrolyte (B), and ozone concentration in the gas phase (C)—was employed to model three responses: pollutant abatement (%), apparent pseudo-first-order rate constant k (min⁻¹), and TOC removal (%). Quadratic models showed good in-samples (R² ≈ 0.84–0.86). Ozone and current dominate abatement and kinetics (with curvature in current), while the electrolyte penalizes mineralization and narrows the window for TOC removal. Under optimal conditions, 116 mA (current), 0.992 mM (electrolyte), and 7.09 ppm (ozone concentration), the EO–O₃ configuration results in a TOC removal of 33.78%. At a reaction time of 10 min (total abatement of the pollutants), the hybrid EO–O₃ configuration exhibits a specific energy consumption (SEC) of 1.825 kWh·m⁻³. We compare trends with the last decade of literature on ozone-based EAOPs, electro-peroxone variants, and BDD anodic oxidation, and outline practical guidance for its application and scale-up, and model refinement in predictive settings. Full article

Background: In Saudi Arabia, rising multi-drug-resistant (MDR) fungal infections from broad-spectrum antifungal overuse highlight the urgent need for epidemiological and susceptibility research. Methods: This cross-sectional study analyzed fungal isolates from 55 patients with positive blood cultures in a Riyadh tertiary hospital, with identification and antifungal susceptibility tested via the VITEK-2 compact system. Results: Candida albicans and non-albicans Candida (NAC) were isolated from 11 and 38 patients, respectively. In the NAC group, C. glabrata and C. parapsilosis spp. were predominant. C. glabrata exhibited the highest resistance to antifungals. Increased rates of resistance were shown by fluconazole and itraconazole, whereas voriconazole was the most effective azole with the lowest resistance. No evidence of resistance was found against non-azole antifungals. A single case of triple resistance to ketoconazole, fluconazole, and itraconazole was observed in C. parapsilosis. A single isolate of C. albicans was resistant to all tested azoles. A rare instance of coinfection with C. glabrata and C. albicans was identified in a single male patient with a dual-resistance pattern against posaconazole and itraconazole. Conclusions: The high prevalence of NAC, including tolerant isolates of C. parapsilosis and C. glabrata, along with multi-azole-resistant C. albicans and unique coinfection scenarios, urgently requires robust antifungal resistance surveillance. Full article

Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from infertile patients for common mycotoxins, including deoxynivalenol (DON), zearalenone (ZEN), its main metabolite alpha-zearalenol (aZOL), and aflatoxin M1 (AfM1), and examined their relationship with oxidative stress markers (MDA, SOD, GPx, CAT, and TAOC) and hormones (cortisol, estradiol, and anti-Müllerian hormone). Higher mycotoxin levels were associated with increased oxidative stress, particularly elevated MDA levels, and disrupted antioxidant enzyme activity. Notably, DON showed a positive correlation with SOD and estradiol levels, indicating a compensatory antioxidant response, while AfM1 served as a negative predictor. The metabolite aZOL was strongly linked to cortisol, with effects influenced by estradiol levels, implying endocrine-disrupting activity. Importantly, the interaction between DON and AMH appeared to impact dominant follicle development, suggesting a potential mechanism by which environmental toxins impair fertility without directly reducing oocyte or embryo counts. These results highlight the complex, dose-dependent effects of mycotoxins on oxidative and hormonal balances within the follicular environment, with implications for oocyte quality and reproductive success. Better understanding these mechanisms could help develop early diagnostic markers and targeted interventions to improve fertility outcomes in women exposed to changing environmental conditions. Full article