History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action

Bioorganic Chemistry, Journal Year: 2020, Volume and Issue: 104, P. 104240 - 104240

Published: Aug. 28, 2020

Language: Английский

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Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.

Language: Английский

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Determination of the Zebrafish Embryo Developmental Toxicity Assessment (ZEDTA) as an Alternative Non-Mammalian Approach for the Safety Assessment of Agrochemicals.

Reproductive Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 108837 - 108837

Published: Jan. 1, 2025

Language: Английский

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Highlighting membrane protein structure and function: A celebration of the Protein Data Bank

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 296, P. 100557 - 100557

Published: Jan. 1, 2021

Biological membranes define the boundaries of cells and compartmentalize chemical physical processes required for life. Many biological are carried out by proteins embedded in or associated with such membranes. Determination membrane protein (MP) structures at atomic near-atomic resolution plays a vital role elucidating their structural functional impact biology. This endeavor has determined 1198 unique MP as early 2021. The value these is expanded greatly deposition three-dimensional (3D) coordinates into Protein Data Bank (PDB) after first structure was elucidated 1985. Since then, free access to facilitates broader deeper understanding MPs, which provides crucial new insights functions. Here we highlight biology representative MPs landmarks evolution technologies, key developments influenced PDB magnifying impact.

Language: Английский

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Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

ACS Omega, Journal Year: 2023, Volume and Issue: 8(4), P. 4369 - 4384

Published: Jan. 19, 2023

Invasive fungal infections (IFIs) are increasing as major infectious diseases around the world, and limited efficacy of existing medications has resulted in substantial morbidity death patients due to lack effective antifungal agents serious drug resistance. In this study, a series benzimidazole-1,2,4-triazole derivatives (6a-6l) were synthesized characterized by 1H NMR, 13C HR-MS spectral analysis. All target compounds screened for their vitro activity against four strains, namely, C. albicans, glabrata, krusei, parapsilopsis. The exhibited significant potential, especially glabrata. Three (6b, 6i, 6j) showed higher with MIC values (0.97 μg/mL) compared voriconazole fluconazole. Molecular docking provided possible binding mode 6b, 6j 14α-demethylase active site. Our studies suggested that can be used new fungicidal lead targeting further structural optimization. addition, effects on L929 cell line also investigated evaluate cytotoxic compounds. SEM analyses performed examine 6a, glabrata cells under vivo experimental conditions.

Language: Английский

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Design, Synthesis, and 3D-QASR of 2-Ar-1,2,3-triazole Derivatives Containing Hydrazide as Potential Fungicides

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(22), P. 12415 - 12424

Published: May 23, 2024

A series of novel 2-Ar-1,2,3-triazole derivatives were designed and synthesized based on our previously discovered active compound 6d against Rhizoctonia solani. Most these compounds exhibited good antifungal activity R. solani at a concentration 25 μg/mL. Based the results biological activity, we established three-dimensional quantitative structure–activity relationship (3D-QSAR) model that guided synthesis 7y. Compound 7y superior (EC50 = 0.47 μg/mL) compared to positive controls hymexazol 12.80 tebuconazole 0.87 μg/mL). Furthermore, demonstrated better protective than aforementioned two commercial fungicides in both detached leaf assays greenhouse experiments, achieving 56.21% 65.75% efficacy, respectively, 100 The ergosterol content was determined molecular docking performed explore mechanism molecules. DFT calculation MEP analysis illustrate this study. These suggest could serve as lead for controlling

Language: Английский

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The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 2, 2025

Language: Английский

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Dimethyl disulfide exerts antifungal activity against Sclerotinia minor by damaging its membrane and induces systemic resistance in host plants

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: April 16, 2020

Abstract Microbial volatile compounds (MVCs) significantly influence the growth of plants and phytopathogens. However, practical application MVCs at field level is limited by fact that concentrations which these antagonize pathogens are often toxic for plants. In this study, we investigated effect dimethyl disulfide (DMDS), one produced microorganisms, on fitness tomato its fungicidal potential against a fungal phytopathogen, Sclerotinia minor . DMDS showed strong plant promoting activities with regard to inhibition mycelial growth, sclerotia formation, germination, reduction disease symptoms in infected S. exposure upregulated expression genes related defense pathogen tomato. Especially, overexpression PR1 PR5 suggested involvement salicylic acid pathway induction systemic resistance. Several morphological ultrastructural changes were observed cell membrane ergosterol biosynthesis gene was downregulated, suggesting damaged membrane, thereby affecting pathogenicity fungus. conclusion, tripartite interaction studies among pathogenic fungus, DMDS, revealed played roles antagonizing as well improving resistance Our findings provide new insights into an effective tool sclerotial rot disease.

Language: Английский

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Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents

European Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 198, P. 112360 - 112360

Published: May 4, 2020

Language: Английский

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Toxicity of the Pesticides Imidacloprid, Difenoconazole and Glyphosate Alone and in Binary and Ternary Mixtures to Winter Honey Bees: Effects on Survival and Antioxidative Defenses

Toxics, Journal Year: 2022, Volume and Issue: 10(3), P. 104 - 104

Published: Feb. 23, 2022

To explain losses of bees that could occur after the winter season, we studied effects insecticide imidacloprid, herbicide glyphosate and fungicide difenoconazole, alone in binary ternary mixtures, on honey orally exposed to food containing these pesticides at concentrations 0, 0.01, 0.1, 1 10 µg/L. Attention was focused bee survival, consumption oxidative stress. The stress were assessed by determining activity enzymes involved antioxidant defenses (superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, peroxidase glucose-6-phosphate dehydrogenase) head, abdomen midgut; damage reflected both lipid peroxidation protein carbonylation also evaluated. In general, no significant effect observed. Pesticide mixtures more toxic than individual substances, highest mortalities induced intermediate doses 0.1 toxicity not always linked exposure level number substances mixtures. Mixtures did systematically induce synergistic effects, as antagonism, subadditivity additivity tested pesticides, triggered important, systemic largely pesticide bees.

Language: Английский

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