Search Results (1,942)

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL⁻¹). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article

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

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

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

Invasive infections with rare yeasts are increasing worldwide and are associated with higher mortality rates due to their resistance to antifungal drugs. Accurate antifungal susceptibility testing (AFST) is crucial for proper management of rare yeast infections. We performed AFST of 74 Candida kefyr isolates by Etest, EUCAST-based MICRONAUT-AM assay (MCN-AM) and reference Clinical and Laboratory Standards Institute broth microdilution method (CLSI). Essential agreement (EA, ±1 two-fold dilution), categorical agreement (CA), major errors (MEs) and very-major errors (VmEs) were determined using epidemiological cut-off values of ≤1.0 µg/mL, ≤0.03 µg/mL, ≤0.5 µg/mL and ≤1 µg/mL, defining wild-type isolates for fluconazole, voriconazole, micafungin and amphotericin B (AMB), respectively. Results for AMB susceptibility were correlated with ERG2/ERG3 mutations and total-cell sterols. CA of ≥97% was recorded between any two methods while EA varied between 72 and 82%, 87 and 92%, and 49 and 76% for fluconazole, voriconazole and micafungin, respectively. For AMB, CAs between CLSI and Etest; CLSI and MCN-AM; MCN-AM and Etest were 95% (4 ME, 0 VmE), 96% (3 ME, 0 VmE) and 99%, respectively, while EA varied from 32% to 69%. Non-synonymous ERG2/ERG3 mutations and no ergosterol were found in seven of eight isolates of non-wild types for AMB by Etest. Our data show that Etest, CLSI and MCN-AM methods are suitable for AFST of C. kefyr for fluconazole, voriconazole and micafungin. Excellent CAs for AMB between Etest and MCN-AM with concordant sterol profiles but not with CLSI suggest that Etest is also an excellent alternative for the detection of C. kefyr isolates with reduced susceptibility to AMB. Full article

Drug resistance in Candida may result in either a fitness cost or a fitness advantage. Candida auris, whose intrinsic drug resistance remains unclear, has emerged as a significant human pathogen. We aimed to investigate whether Candida fitness, including early interaction with the host innate immune system, depends on the antifungal susceptibility phenotype and putative-associated resistance mutations. We compared interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor α production by human colorectal adenocarcinoma cells stimulated by fluconazole-susceptible and fluconazole-resistant strains of Candida albicans, C. parapsilosis, C. tropicalis, and C. glabrata, as well as fluconazole-resistant C. auris strains. Sensitive Candida strains induced lower cytokine levels compared with C. auris and resistant strains, except for TNF a. Resistant strains induced cytokine levels like C. auris, except for higher IL-1β and lower TNF-α. Susceptible strains exhibited cytokine profiles distinct from those of resistant strains. C. auris induced cytokine levels comparable to resistant strains but displayed profiles resembling those of susceptible strains. This study highlights the relationship among antifungal susceptibility, fungal fitness and host early immunity. C. auris behavior appears to be between fluconazole-sensitive and fluconazole-resistant strains. Understanding these dynamics may enhance the knowledge of the survival and reproduction of resistant Candida and the epidemiology of fungal infections. Full article

Beach Sand Mycobiome is currently among the most important health challenges for viticulture in the world. Remarkably, the study of fungal communities in coastal beach sand and recreational waters remains underexplored despite their potential implications for human health. This research aimed to assess the prevalence of fungal species and the antifungal susceptibility profiles of fungi recovered from the beaches of the Persian Gulf and the Sea of Oman. Sand and seawater samples from 39 stations distributed within 13 beaches along the coastline were collected between May and July 2023. The grown isolates were identified at the species level based on morphological characteristics and DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical Laboratory Standards Institute guidelines. Of 222 recovered isolates, 206 (92.8%) filamentous fungi and 16 (7.2%) yeast strains were identified. Sand-recovered fungi comprised 82.9%, while water-originated fungi accounted for 17.1%. The DNA sequencing technique categorized 191 isolates into 13 genera and 26 species. The most recovered genus was Aspergillus (68.9%), and Aspergillus terreus sensu stricto was the commonly identified species (26.14%). Voriconazole was the most effective antifungal drug against Aspergillus species. Research on fungal contamination levels at these locations could provide a foundation for establishing regulatory frameworks to diminish fungal risks, thereby enhancing public health protection. The ecological significance of fungal communities in sandy beaches to human infections remains to be explored, and earlier reports in the literature may motivate researchers to focus on detecting this mycobiome in natural environments where further investigation is warranted. Ultimately, our discovery serves as a reminder that much remains to be learned about pathogenic fungi and underscores the need for vigilance in areas where emerging pathogens have not yet been identified. Full article

The use of metal-based complexes is currently taking centre stage in the field of nanomedicine for the treatment and control of various ailments. Rhenium(I) tricarbonyl complexes have frequently been evaluated in vitro for their anticancer activities, and a few have advanced to in vivo and clinical trials, owing to the distinct application characteristics of these complexes. Their inception in drug development is key. This study explores a detailed chronological overview of the medical applications of Re(I) tricarbonyl complexes over the past six years (2019–2024), focusing on their applications and clinical tests in the control and management of various ailments. An in-depth examination of their activities in anticancer treatments, Chagas disease, antifungal infections, antimalarial, and microbial infections was conducted, comparing the complexes to various standard antibiotics, conventional antimalarial drugs, antifungals, and standard anticancer agents. Full article

With the rise in immunocompromised individuals and patients with immune-related comorbidities such as COVID-19, the rate of fungal infections is growing. This increase, along with the current plateau in antifungal drug development, has made understanding the pathogenesis and dissemination of these organisms more pertinent than ever. The mouse model of fungal infection, while informative on a basic scientific level, has severe limitations in terms of translation to the human disease. Here we present data supporting the implementation of the human cerebral organoid model, which is generated from human embryonic stem cells and accurately recapitulates relevant brain cell types and structures, to study fungal infection and dissemination to the central nervous system (CNS). This approach provides direct insight into the relevant pathogenesis of specific fungal organisms in human tissues where in vivo models are impossible. With this model system we assessed the specific brain tropisms and cellular effects of fungal pathogens known to cross the blood–brain barrier (BBB), such as Cryptococcus neoformans. We determined the effects of this fungal pathogen on the overall gross morphology, cellular architecture, and cytokine release from these model organoids. Furthermore, we demonstrated that C. neoformans penetrates and invades the organoid tissue and remains present throughout the course of infection. These results demonstrate the utility of this new model to the field and highlight the potential for this system to elucidate fungal pathogenesis to develop new therapeutic strategies to prevent and treat the disseminated stages of fungal diseases such as cryptococcal meningitis. Full article

Since the approval of Bortezomib (Velcade^®) by the U.S. Food and Drug Administration (FDA) in 2003, boron-containing drugs have successfully entered the global market, spanning therapeutic areas such as anticancer, antibacterial, and antifungal agents. Meanwhile, boron is an essential trace element for plant growth, and boronic acid has been widely used as plant resistance inducers and growth promoters. In 2024, the Fungicide Resistance Action Committee (FRAC) introduced benzoxaboroles as a new category of fungicides, which fully demonstrates the significant application potential of boron-containing compounds (BCCs) in the field of agricultural fungicides. Recently, studies on BCCs in agriculture have emerged continuously. Compared with the systematic reviews in the pharmaceutical field, those focusing on BCCs in agriculture remain absent. This review systematically collates BCCs with reported biological activities from the literature over the past 20 years, from the perspective of boron-containing building blocks. It mainly focuses on the potential of boronic acid derivatization and its activities in agrochemicals. Additionally, it covers the applications of boron-containing building blocks in pharmaceuticals, including their action mechanisms. Full article

Background: Fungal infections, particularly those caused by Candida species, pose a serious threat to immunocompromised individuals, and therapeutic options are limited due to toxicity and resistance concerns. This in vitro study aimed to explore the feasibility of using liquid fractions of autologous platelet concentrates (APCs), namely concentrated platelet-rich fibrin (c-PRF) and liquid-phase concentrated growth factor (LPCGF), as carriers for antifungal drugs. Methods: The research was conducted in two phases: first, to evaluate the inherent antifungal properties of different APCs; and second, to assess their effectiveness as drug carriers for fluconazole and voriconazole against Candida albicans, Candida glabrata, and Candida krusei. Results: Results showed that APCs alone exhibited no direct antifungal effects. However, when combined with antifungal agents, notable inhibition zones were observed—especially with voriconazole against C. krusei and fluconazole against C. glabrata using c-PRF. Both c-PRF and LPCGF were compatible with the drugs and did not hinder clot formation. Conclusions: These findings suggest that APCs can act as effective vehicles for localized antifungal drug delivery and warrant further investigation for clinical application in treating fungal-related oral diseases. Full article

This study focuses on the search for new effective synthetic antimicrobial compounds as a tool against the widespread presence of microorganisms resistant to existing drugs. Five derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazoles were synthesized using an accessible protocol based on electrophilic heterocyclization and were characterized using infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, and their in vitro antimicrobial and antifungal activities were evaluated using the agar plate diffusion method and the microdilution plate procedure. Both antibacterial (Gram-positive and Gram-negative) and antifungal activities were found for the examined samples. The minimum inhibitory concentration (MIC) varied from 0.97 to 250 µg/mL, and the minimum bactericidal concentration (MBC) from 1.95 to 500 µg/mL. Compound 2a showed good antifungal action against Candida albicans and Saccharomyces cerevisiae with minimum fungicidal concentration (MFC) 125 and MIC 31.25 µg/mL. The molecular docking revealed that the 2-heptyl-3-phenyl-6,6-trimethyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium cation stands out as a highly promising candidate for further investigation due to a wide range of interactions, including conventional hydrogen bonds, π–σ, π–π T-shaped, and hydrophobic alkyl interactions. The synthesis and preliminary evaluation of [1,3]thiazolo[3,2-b][1,2,4]triazoles yielded promising antimicrobial and antifungal candidates. The diverse interaction profile of the 2-heptyl derivative salt allows this compound’s selection for further biological studies. Full article

This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion. Full article

Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, wound healing, acne management, and cosmetic dermatology. Zeolites demonstrated broad-spectrum antibacterial and antifungal efficacy, enhanced antioxidant activity, and biocompatible drug delivery in various dermatological models. Formulations such as silver–sulfadiazine–zeolite composites, Zn–clinoptilolite for acne, and zeolite-integrated microneedles offer innovative avenues for targeted therapy. Zeolite-based systems represent a promising shift toward multifunctional, localized dermatologic treatments. However, further research into long-term safety, formulation optimization, and clinical validation is essential to transition these materials into mainstream therapeutic use. Full article