Synthesis of New Azoles For the Treatment of Resistant Infections Caused By Who Critical Priority Fungi: Therapeutic Challenges and Innovations in The Fight Against Them DOI Creative Commons
Amanda Vieira de Barros, José Henrique Serafim Batista da Silva, Isabela Ribeiro

и другие.

Revista de Gestão Social e Ambiental, Год журнала: 2025, Номер 19(3), С. e011670 - e011670

Опубликована: Март 20, 2025

Objective: The study aimed to conduct a review of new azoles derivatives tackle the critical priority pathogens World Health Organization (WHO). Theoretical background: Azoles are main class antifungal drugs, and creation drugs based on their fundamental structure could be viable alternative for combating listed by WHO as due high mortality resistance. Method: used databases such PubMed, Scopus Science Direct, with articles published between 2019 2024. Papers addressing infections caused these fungi azole an against were included, 20 selected. Results discussion: list highlights Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus auris, which in urgent need therapeutic alternatives. Experimental studies have revealed significant advances structural modification azoles, especially relation hybrid compounds combining triazole oxadiazole nuclei containing hydrophobic substituents, broad spectrum mechanisms action. Research implications: Resistance has increased globally threatens effectiveness available treatments. synthesis can help fill gaps, modifications serve basis development improved Originality value: Novel molecules, combination cores, introduction groups, not only increase efficacy, but also improve penetration into biofilms thermal stability. These innovations represent advance treatment fungal therapies.

Язык: Английский

Organ-on-chip models for infectious disease research DOI
Raquel Alonso‐Román, Alexander S. Mosig, Marc Thilo Figge

и другие.

Nature Microbiology, Год журнала: 2024, Номер 9(4), С. 891 - 904

Опубликована: Март 25, 2024

Язык: Английский

Процитировано

23
New treatment options for critically important WHO fungal priority pathogens DOI Creative Commons
Lisa Kriegl, Matthias Egger, Johannes Boyer

и другие.

Clinical Microbiology and Infection, Год журнала: 2024, Номер unknown

Опубликована: Март 1, 2024

BackgroundYet often overlooked in public health discourse, fungal infections pose a crucialglobal disease burden associated with annual mortality rates approximately equal to tuberculosis and HIV. In response, the World Health Organization (WHO) published its first global priority list of pathogens 2022 assigning Aspergillus fumigatus, Candida albicans, auris, Cryptococcus neoformans critical group.ObjectivesThis review provides succinct insights on novel antifungals development, aiming contribute valuable information perspectives focus recent clinical findings new treatment approaches for members WHO pathogen list.SourcesPubMed literature search using "Aspergillus fumigatus," "Cryptococcus neoformans," "Candida auris," albicans," along names antifungal substances, including "fosmanogepix", "ibrexafungerp", "opelconazole", "oteseconazole", "MAT2203", "olorofim", "rezafungin" was conducted.ContentForeach pathogen, current issues data from trials are covered. The remarkable development three therapeutics recently receiving Food Drug Administration (FDA) approval (ibrexafungerp -June 2021, oteseconazole -April 2022, rezafungin -March 2023) is outlined, two more exciting namely olorofim fosmanogepix expecting within next years. Ibrexafungerp, have additionally been granted orphan drug status by European Medicines Agency (EMA) Europe -November -July -January 2024).ImplicationsWhile limited number targets emergence resistance posed challenges treatment, drugs such as ibrexafungerp, rezafungin, fosmanogepix, or shown promising efficacy. These not only provide alternative options invasive but also alleviate outpatient settings. More data, implementation stewardship programs, surveillance, utilization agriculture necessary prevent ensure safety efficacy these agents.

Язык: Английский

Процитировано

18
A polyene macrolide targeting phospholipids in the fungal cell membrane DOI Creative Commons
Qun Deng, Y. Li,

Wenyan He

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

The global spread of multidrug-resistant pathogenic fungi presents a serious threat to human health, necessitating the discovery antifungals with unique modes action1. However, conventional activity-based screening for previously undescribed antibiotics has been hampered by high-frequency rediscovery known compounds and lack new antifungal targets2. Here we report polyene antibiotic, mandimycin, using phylogeny-guided natural-product platform. Mandimycin is biosynthesized mand gene cluster, evolved in distinct manner from macrolide modified three deoxy sugars. It demonstrated potent broad-spectrum fungicidal activity against wide range fungal pathogens both vitro vivo settings. In contrast that target ergosterol, mandimycin mode action involves targeting various phospholipids cell membranes, resulting release essential ions cells. This ability bind multiple targets gives it robust as well capability evade resistance. identification strategy represents an important advancement uncovering antimicrobial action, which could be developed combat pathogens. Mandimycin, macrolide, exhibits strong possesses other this class.

Язык: Английский

Процитировано

2
Fungicide-tolerant persister formation during cryptococcal pulmonary infection DOI Creative Commons
Weixin Ke,

Yuyan Xie,

Yingying Chen

и другие.

Cell Host & Microbe, Год журнала: 2024, Номер 32(2), С. 276 - 289.e7

Опубликована: Янв. 11, 2024

Язык: Английский

Процитировано

14
Antifungal Resistance in Cryptococcal Infections DOI Creative Commons
Márcia de Souza Carvalho Melhem, Diniz Pereira Leite Júnior, Juliana Possatto Fernandes Takahashi

и другие.

Pathogens, Год журнала: 2024, Номер 13(2), С. 128 - 128

Опубликована: Янв. 29, 2024

Antifungal therapy, especially with the azoles, could promote incidence of less susceptible isolates Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these affect immunocompromised host, infections are severe difficult to treat. This review encompasses following topics: 1. infecting their virulence, 2. treatment, 3. antifungal susceptibility methods available categorical endpoints, 4. genetic mechanisms resistance, 5. clinical 6. fluconazole minimal inhibitory concentrations (MICs), outcome, 7. environmental influences, 8. relevance host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, predicting outcome therapy. As now, epidemiologic cutoff endpoints (ECVs/ECOFFs) most reliable resistance detectors for species, as only one breakpoint (amphotericin B VNI) is available.

Язык: Английский

Процитировано

8
Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications DOI Open Access
Steward Mudenda

Pharmacology &amp Pharmacy, Год журнала: 2024, Номер 15(04), С. 81 - 112

Опубликована: Янв. 1, 2024

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires One Health approach including Stewardship (AFS). This study aimed to comprehensively review studies published on fungal infections and recommend solutions address this growing problem. Materials Methods: was narrative that conducted using papers infections, AFR, AFS between January 1961 March 2024. The literature searched PubMed, Google Scholar, Web of Science, EMBASE. Results: found there has been an increase in globally, patients. Due proportionate the use antifungal agents prevent treat infections. increased worsened contributing morbidity mortality. Globally, have contributed 150 million annually 1.7 deaths per year. By year 2023, over 3.8 people died from remains challenge because treatment antifungal-resistant difficult. Finally, exacerbated by limited number invasive Conclusion: results indicated are prevalent across humans, animals, agriculture, environment. provision such as improving awareness conducting further research discovery new agents, implementing programs. If not addressed, mortality associated will continue rise future.

Язык: Английский

Процитировано

8
A Mechanistic Overview on Green Assisted Formulation of Nanocomposites and Their Multifunctional Role in Biomedical Applications DOI Creative Commons

Mahnoor Mahnoor,

Khafsa Malik, Abeer Kazmi

и другие.

Heliyon, Год журнала: 2025, Номер 11(3), С. e41654 - e41654

Опубликована: Янв. 8, 2025

The importance of nanocomposites constantly attains attention because their unique properties all across the fields especially in medical perspectives. study green-synthesized has grown to be extremely fascinating field research. Nanocomposites are more promising than mono-metallic nanoparticles they exhibit synergistic effects. This review encapsulates current development formulation plant-mediated by using several plant species and impact secondary metabolites on biocompatible functioning. Phyto-synthesis produces diverse nanomaterials with biocompatibility, environment-friendliness, vivo actions, characterized varying sizes, shapes, biochemical nature. process is advantageous conventional physical chemical procedures. New studies have been conducted determine biomedical efficacy against various diseases. Unfortunately, there inadequate investigation into green-assisted nanocomposites. Incorporating phytosynthesized therapeutic interventions not only enhances healing processes but also augments host's immune defenses infections. highlights phytosynthesis applications, including antibacterial, antidiabetic, antiviral, antioxidant, antifungal, anti-cancer, other as well toxicity. explores mechanistic action achieve designated tasks. Biogenic for multimodal imaging potential exchange methods materials Well-designed utilized innovative theranostic agents subsequent objective efficiently diagnosing treating a variety human disorders.

Язык: Английский

Процитировано

1
Natural Polyketides Act as Promising Antifungal Agents DOI Creative Commons
Li Wang, Hui Lu,

Yuanying Jiang

и другие.

Biomolecules, Год журнала: 2023, Номер 13(11), С. 1572 - 1572

Опубликована: Окт. 24, 2023

Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited range, inadequate safety profiles, and low oral bioavailability. Consequently, there an urgent imperative develop novel medications for clinical application. This comprehensive review provides summary the properties mechanisms exhibited natural polyketides, encompassing macrolide polyethers, polyether xanthone linear hybrid polyketide non-ribosomal peptides, pyridine derivatives. Investigating compounds their derivatives has demonstrated remarkable efficacy promising application as agents.

Язык: Английский

Процитировано

16
Climate Change Exacerbating Fungal Disease Disparities DOI
Alexandro Bonifáz,

Eduardo García-Salazar,

María Guadalupe Frías‐De‐León

и другие.

Current Fungal Infection Reports, Год журнала: 2024, Номер 18(1), С. 1 - 12

Опубликована: Янв. 16, 2024

Язык: Английский

Процитировано

4
Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal DOI Creative Commons
Raquel Fernandes, Raquel Sabino, Cristina Cunha

и другие.

Mycopathologia, Год журнала: 2024, Номер 189(1)

Опубликована: Янв. 24, 2024

Abstract The success of the clinical management invasive fungal diseases (IFD) is highly dependent on suitable tools for timely and accurate diagnosis effective treatment. An in-depth analysis ability European institutions to promptly accurately diagnose IFD was previously conducted identify limitations aspects improve. Here, we evaluated discussed specific case Portugal, which, our knowledge, there are no reports describing national mycological diagnostic capacity access antifungal Data from 16 Portuguese medical were collected via an online electronic report form covering different parameters, including institution profile, self-perceived incidence, target patients, methods reagents, available antifungals. majority participating (69%) reported a low-very low incidence IFD, with Candida spp. indicated as most relevant pathogen, followed by Aspergillus Cryptococcus All had culture microscopy, whereas 94 88% able run antigen-detection assays molecular tests, respectively. capable providing therapy declared have at least one antifungal. However, echinocandins only 85% sites. Therapeutic drug monitoring (TDM) remain very restricted practice in being 19% institutions, TDM itraconazole posaconazole performed 6% them. Importantly, several these resources outsourced external entities. Except TDM, Portugal appears be well-prepared concerning overall treat IFD. Future efforts should focus promoting widespread availability improved multiple classes antifungals, further improve patient outcomes.

Язык: Английский

Процитировано

4