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International Journal of Molecular... Aug 2022Mycoses are accountable for millions of infections yearly worldwide. Invasive candidiasis is the most usual, presenting a high morbidity and mortality. remains the... (Review)
Review
Mycoses are accountable for millions of infections yearly worldwide. Invasive candidiasis is the most usual, presenting a high morbidity and mortality. remains the prevalent etiologic agent, but the incidence of other species such as , and keeps increasing. These pathogens frequently show a reduced susceptibility to commonly used antifungal drugs, including polyenes, triazoles and echinocandins, and the incidence of emerging multi-drug-resistant strains of these species continues to increase. Therefore, the need to search for new molecules that target these pathogenic species in a different manner is now more urgent than ever. Nature is an almost endless source of interesting new molecules that could meet this need. Among these molecules, antimicrobial peptides, present in different sources in nature, possess some advantages over conventional antifungal agents, even with their own drawbacks, and are considered as a promising pharmacological option against a wide range of microbial infections. In this review, we describe 20 antimicrobial peptides from different origins that possess an activity against .
Topics: Antifungal Agents; Antimicrobial Peptides; Candida; Candidiasis, Invasive; Drug Resistance, Fungal; Echinocandins; Microbial Sensitivity Tests
PubMed: 36012523
DOI: 10.3390/ijms23169264 -
Biomolecules Oct 2023Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range,... (Review)
Review
Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range, inadequate safety profiles, and low oral bioavailability. Consequently, there is an urgent imperative to develop novel antifungal medications for clinical application. This comprehensive review provides a summary of the antifungal properties and mechanisms exhibited by natural polyketides, encompassing macrolide polyethers, polyether polyketides, xanthone polyketides, linear polyketides, hybrid polyketide non-ribosomal peptides, and pyridine derivatives. Investigating natural polyketide compounds and their derivatives has demonstrated their remarkable efficacy and promising clinical application as antifungal agents.
Topics: Humans; Antifungal Agents; Polyketides; Macrolides; Peptides
PubMed: 38002254
DOI: 10.3390/biom13111572 -
The Journal of Antimicrobial... Nov 2022Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In...
Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.
Topics: Humans; Mycoses; Antifungal Agents; Invasive Fungal Infections; Azoles; Fungi; Pulmonary Aspergillosis; COVID-19 Drug Treatment
PubMed: 36426674
DOI: 10.1093/jac/dkac353 -
Frontiers in Cellular and Infection... 2020Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes... (Review)
Review
Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes of relevance to the bioeconomy. Moreover, they are starting to gain attention as a key component of the human microbiome. However, fungi are also responsible for human infections. The incidence of community-acquired and nosocomial fungal infections has increased considerably in recent decades. Antibiotic resistance development, the increasing number of immunodeficiency- and/or immunosuppression-related diseases and limited therapeutic options available are triggering the search for novel alternatives. These new antifungals should be less toxic for the host, with targeted or broader antimicrobial spectra (for diseases of known and unknown etiology, respectively) and modes of actions that limit the potential for the emergence of resistance among pathogenic fungi. Given these criteria, antimicrobial peptides with antifungal properties, i.e., antifungal peptides (AFPs), have emerged as powerful candidates due to their efficacy and high selectivity. In this review, we provide an overview of the bioactivity and classification of AFPs (natural and synthetic) as well as their mode of action and advantages over current antifungal drugs. Additionally, natural, heterologous and synthetic production of AFPs with a view to greater levels of exploitation is discussed. Finally, we evaluate the current and potential applications of these peptides, along with the future challenges relating to antifungal treatments.
Topics: Antifungal Agents; Fungi; Humans; Mycoses; Peptides; Pharmaceutical Preparations
PubMed: 32257965
DOI: 10.3389/fcimb.2020.00105 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2023Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water... (Review)
Review
Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Topics: Antifungal Agents; Drug Delivery Systems; Amphotericin B; Liposomes; Nanoparticles; Drug Carriers
PubMed: 37476943
DOI: 10.3724/zdxbyxb-2023-0030 -
International Journal of Molecular... Nov 2021Compounds of natural origin, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovering new medicines. In this review, we... (Review)
Review
Compounds of natural origin, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovering new medicines. In this review, we summarize the naturally occurring ellagitannins, sanguiins, which are bioactive constituents of various traditional medicinal plants, especially from the Rosaceae family. In-depth studies of sanguiin H-6 as an antimicrobial, antiviral, anticancer, anti-inflammatory, and osteoclastogenesis inhibitory agent have led to potent drug candidates. In addition, recently, virtual screening studies have suggested that sanguiin H-6 might increase resistance toward SARS-CoV-2 in the early stages of infection. Further experimental investigations on ADMET (absorption, distribution, metabolism, excretion, and toxicity) supplemented with molecular docking and molecular dynamics simulation are still needed to fully understand sanguiins' mechanism of action. In sum, sanguiins appear to be promising compounds for additional studies, especially for their application in therapies for a multitude of common and debilitating ailments.
Topics: Animals; Antifungal Agents; Antineoplastic Agents; Antiviral Agents; Humans; Hydrolyzable Tannins; Molecular Docking Simulation; Molecular Dynamics Simulation; Pharmacokinetics; Rosaceae; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34884795
DOI: 10.3390/ijms222312972 -
BioMed Research International 2022The development of innovative antifungal agents is essential. Some fungicidal agents are no longer effective due to resistance development, various side effects, and... (Review)
Review
The development of innovative antifungal agents is essential. Some fungicidal agents are no longer effective due to resistance development, various side effects, and high toxicity. Therefore, the synthesis and development of some new antifungal agents are necessary. 1,2,4-Triazole is one of the most essential pharmacophore systems between five-membered heterocycles. The structure-activity relationship (SAR) of this nitrogen-containing heterocyclic compound showed potential antifungal activity. The 1,2,4-triazole core is present as the nucleus in a variety of antifungal drug categories. The most potent and broad activity of triazoles have confirmed them as pharmacologically significant moieties. The goal of this review is to highlight recent developments in the synthesis and SAR study of 1,2,4-triazole as a potential fungicidal compound. In this study, we provide the results of a biological activity evaluation using various structures and figures. Literature investigation showed that 1, 2, 4-triazole derivatives reveal the extensive span of antifungal activity. This review will assist researchers in the development of new potential antifungal drug candidates with high effectiveness and selectivity.
Topics: Antifungal Agents; Microbial Sensitivity Tests; Structure-Activity Relationship; Triazoles
PubMed: 35360519
DOI: 10.1155/2022/4584846 -
Biomolecules Oct 2023This comprehensive review examines iturin, a cyclic lipopeptide originating from and related bacteria. These compounds are structurally diverse and possess potent... (Review)
Review
This comprehensive review examines iturin, a cyclic lipopeptide originating from and related bacteria. These compounds are structurally diverse and possess potent inhibitory effects against plant disease-causing bacteria and fungi. Notably, Iturin A exhibits strong antifungal properties and low toxicity, making it valuable for bio-pesticides and mycosis treatment. Emerging research reveals additional capabilities, including anticancer and hemolytic features. Iturin finds applications across industries. In food, iturin as a biosurfactant serves beyond surface tension reduction, enhancing emulsions and texture. Biosurfactants are significant in soil remediation, agriculture, wound healing, and sustainability. They also show promise in Microbial Enhanced Oil Recovery (MEOR) in the petroleum industry. The pharmaceutical and cosmetic industries recognize iturin's diverse properties, such as antibacterial, antifungal, antiviral, anticancer, and anti-obesity effects. Cosmetic applications span emulsification, anti-wrinkle, and antibacterial use. Understanding iturin's structure, synthesis, and applications gains importance as biosurfactant and lipopeptide research advances. This review focuses on emphasizing iturin's structural characteristics, production methods, biological effects, and applications across industries. It probes iturin's antibacterial, antifungal potential, antiviral efficacy, and cancer treatment capabilities. It explores diverse applications in food, petroleum, pharmaceuticals, and cosmetics, considering recent developments, challenges, and prospects.
Topics: Antifungal Agents; Bacillus subtilis; Lipopeptides; Anti-Bacterial Agents; Antiviral Agents
PubMed: 37892197
DOI: 10.3390/biom13101515 -
Antimicrobial Agents and Chemotherapy Oct 2023() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is...
() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.
Topics: Humans; Mice; Animals; Meningitis, Cryptococcal; Antifungal Agents; Cryptococcus neoformans; Cryptococcosis; Amphotericin B; Flucytosine; Meningoencephalitis
PubMed: 37750714
DOI: 10.1128/aac.00459-23 -
Frontiers in Cellular and Infection... 2022Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a... (Review)
Review
PURPOSE
Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD.
METHODS
We performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review.
RESULTS
IFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD.
CONCLUSION
Taken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions.
Topics: Humans; Triazoles; Invasive Fungal Infections; Nitriles; Antifungal Agents; Aspergillosis; Mucormycosis; Candidiasis, Invasive
PubMed: 36530445
DOI: 10.3389/fcimb.2022.1049959