Marine-Derived Metabolites Act as Promising Antifungal Agents

Marine Drugs, Год журнала: 2024, Номер 22(4), С. 180 - 180

Опубликована: Апрель 17, 2024

The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, echinocandins, face increasing resistance from pathogenic fungi. Therefore, there a pressing need for development novel drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures pharmacological activities. While numerous compounds exhibiting promising activity have been identified, comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we compiled summary derived marine organisms, highlighting diverse action targeting various cellular components, including cell wall, membrane, mitochondria, chromosomes, drug efflux pumps, several biological processes, vesicular trafficking growth hyphae biofilms. This helpful subsequent drugs due its organisms.

Язык: Английский

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Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species

Antioxidants, Год журнала: 2024, Номер 13(6), С. 667 - 667

Опубликована: Май 29, 2024

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, fungistatic nature FLC renders pathogenic fungi capable developing tolerance towards it. Consequently, converting into a fungicidal agent using adjuvants assumes significance to circumvent resistance perpetuation infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as promising adjuvant enhancing activity from comprehensive library 2372 FDA-approved drugs. PIT could render even at concentrations low 1 μM. The median lethal dose (LD50) was determined be 103.6 mg/kg. We have discovered that achieves its synergistic effect by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, disrupting Golgi function. Candida albicans strain demonstrated notable infect mice found effectively augmented antifungal efficacy against IFIs. an illustrative example how drugs can eliminate FLC.

Язык: Английский

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Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms

Chinese Herbal Medicines, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The mechanism of action traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused exploring the mechanisms active components acting single targets. However, it is insufficient to explain complex by which these in treat diseases. In recent years, emergence molecular glues (MGs) theory provided new strategies address this issue. MGs are small molecules that can promote interactions between proteins at their interface. characteristic establish connections diverse protein structures, thereby enabling a chemically-mediated proximity effect triggers wide spectrum biological functions. Natural products result billions years evolutionary processes natural environment. Thus, extensive structural diversity renders them rich source MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known immunosuppressants cyclosporin A (CsA) tacrolimus (FK506), as well anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, advancement technologies propelling discovery novel from products. we primarily summarize growing variety origins reported categorize based chemical types. Moreover, main sources promises provide perspective for elucidation behind efficiency TCM. summary, review aims insights could potentially influence modern drug development.

Язык: Английский

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Extracellular fungal Hsp90 represents a promising therapeutic target for combating fungal infections

European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 207, С. 107041 - 107041

Опубликована: Фев. 12, 2025

Heat shock protein 90 (Hsp90) is a pivotal virulence factor in pathogenic fungi, playing significant role conferring drug resistance. However, due to the high amino acid sequence similarity between fungal and mammalian Hsp90, targeting intracellular Hsp90 therapeutically associated with marked toxic side effects, thereby limiting clinical application. Studies have demonstrated that can be secreted as extracellular (eHsp90), which plays crucial infections. Strategies eHsp90 exhibited promising therapeutic outcomes. Unlike targeting, such antifungal approaches operate without cell penetration, circumventing effects Hsp90's conservation. This review summarizes potential secretion pathways of eHsp90, its roles pathogenesis, well development vaccines antibodies eHsp90. The underlines significance infections suggests represents target for infection treatment.

Язык: Английский

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Cu²⁺-Cross-Linked Tannic Acid Carbon Dot Nanoparticles for Mold Inhibition

ACS Applied Nano Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Mold has long been a priority because of its potential threat to human health and reduction in the value wood. Most traditional mold inhibitors have toxic effects on environment, so developing safe nontoxic remains challenge. In this study, tannic acid carbon dots (TA-CDs) were obtained via straightforward one-step hydrothermal process. Subsequently, Cu2+ cross-linked dot nanoparticles (TA-CDs-Cu2+) synthesized by introducing TA-CDs at room temperature. The TA-CDs-Cu2+ can be firmly anchored surface Aspergillus niger spores, triggering rapid release localized acidic environment. released triggered conversion Cu+, destroying cell wall membrane structure A. reducing cellular esterase activity. addition, demonstrated diminish biomass biofilms markedly. use poplar birch wood achieved protection class 0 20 mg Cu/mL, which found exhibit unparalleled advantages as inhibitor. Meanwhile, warming effect opened up avenues for design inhibition therapeutic agents photothermal synergistic inhibition.

Язык: Английский

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The pks1 gene encodes non-reducing polyketone synthetase involved in anthraquinones biosynthesis in M. purpureus YY-1

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 141399 - 141399

Опубликована: Фев. 1, 2025

Язык: Английский

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Genome characterisation of three mycorrhizal helper bacterial strains isolated from a polycyclic aromatic hydrocarbon polluted site

Molecular Genetics and Genomics, Год журнала: 2025, Номер 300(1)

Опубликована: Фев. 22, 2025

Язык: Английский

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Bioactive Molecules of Microbial Origin

Опубликована: Янв. 1, 2025

Язык: Английский

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Analysis of metabolic differences in Tibetan medicinal plant Phlomoides rotata leaves in different habitats based on non-targeted metabolomics

Frontiers in Plant Science, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Phlomoides rotata , a traditional Tibetan medicinal herb renowned for its anti-inflammatory and analgesic properties, exhibits distinct metabolite profiles across heterogeneous environments. However, the impacts of altitude slope orientation on secondary metabolism remain poorly understood. This study aimed to characterize variations in leaves under different elevations microclimates, providing mechanistic basis quality evaluation sustainable utilization. Metabolomic analysis was conducted using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-MS). Leaf samples were collected from three gradients (4,300 m, 4,600 5,000 m) two orientations (south vs. north) Budanla Mountain, Qusong County, Shannan, Xizang Autonomous Region, China. A total 2,331 metabolites detected, with lipids (41.93%), organic oxygen compounds (13.95%), phenylpropanoids (12.4%) dominating profile. Altitudinal induced significant changes 5 differentially accumulated (DAMs), including procyanidin B2 dihydrocoumarin. Slope influenced 17 DAMs, such as 2,3-secoporrigenin 2-O-α-D-galactopyranosyl-1-deoxynojirimycin. Kyoto Encyclopedia Genes Genomes (KEGG) enrichment revealed altitude-specific flavonoid biosynthesis pantothenate/CoA biosynthesis, while slope-related DAMs enriched glycerophospholipid galactose metabolism. Altitude-driven increases flavonoids (e.g., B2) likely reflect adaptive responses UV radiation oxidative stress. Slope-related shifts, particularly glycerophospholipids, may relate microclimate differences temperature moisture. These findings highlight critical role environmental factors shaping metabolic phenotype implications pharmacologically active compound biosynthesis. The identified serve potential biomarkers control, pathway provides targets engineering conservation cultivation practices.

Язык: Английский

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Linking a polyketide synthase gene cluster to 6-pentyl-alpha-pyrone, a Trichoderma metabolite with diverse bioactivities

Microbial Cell Factories, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 21, 2025

Abstract Background Members of the fungal genus Trichoderma are well-known for their mycoparasitic and plant protecting activities, rendering them important biocontrol agents. One most significant specialized metabolites (SMs) produced by various species is unsaturated lactone 6-pentyl-alpha-pyrone (6-PP). Although first identified more than 50 years ago having pronounced antifungal growth-promoting properties, biosynthetic pathway 6-PP still remains unresolved. Results Here, we demonstrate that biosynthesized via polyketide biosynthesis pathway. We Pks1, an iterative type I synthase, as crucial its in atroviride , a recognized prominent production abilities. Phylogenetic comparative genomic analyses revealed pks1 gene part cluster conserved those known to produce 6-PP. Deletion caused complete loss T. reduction activity against Botrytis cinerea Rhizoctonia solani . Surprisingly, absence led enhanced lateral root formation Arabidopsis thaliana during interaction with Transcriptomic analysis co-regulation adjacent genes, including candidates coding C3H1-type zinc finger protein lytic polysaccharide monooxygenase, suggesting coordination between environmental response mechanisms. Conclusion Our findings establish essential providing novel insights into one compounds this mycoparasite. These may pave way development improved agents application potent biopesticide contributing eco-friendly sustainable disease management.

Язык: Английский

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