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Elucidating the mechanism of action of an antifungal or cytotoxic compound is a time-consuming process. Yeast chemogenomic profiling provides a compelling solution to the problem but is experimentally complex. Here, we demonstrate the use of a highly simplified yeast chemical genetic assay comprising just 89 yeast deletion strains, each diagnostic for a specific mechanism of action. We use the assay to investigate the mechanism of action of two antifungal chalcone compounds, trans-chalcone and 4'-hydroxychalcone, and narrow down the mechanism to transcriptional stress. Crucially, the assay eliminates mechanisms of action such as topoisomerase I inhibition and membrane disruption that have been suggested for related chalcone compounds. We propose this simplified assay as a useful tool to rapidly identify common off-target mechanisms.
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http://dx.doi.org/10.1002/1873-3468.14483 | DOI Listing |
Chem Biodivers
September 2025
Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, Laboratory of Anti-Allergy Functional Compounds, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
Autoimmune diseases (AIDs), defined by irregularities in immune system function, pose a substantial health challenge worldwide, impacting millions with persistent and frequently debilitating conditions. Conventional treatments, such as glucocorticoid-based immunosuppressive therapies, are associated with notable drawbacks and limitations. In response to these difficulties, recent scientific efforts have increasingly focused on natural compounds as potential therapeutic agents.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
College of Forestry, East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration; Jiangxi Provincial Key Laboratory of Improved Variety Breeding and Efficient Utilization of Native Tree Species, Jiangxi Agricultural University, Nanchang 330045,
To discover novel preservatives for treating wood-decaying fungi, 48 novel eugenol quaternary ammonium salt derivatives were designed and synthesized. Among them, compounds , , , , , , and showed remarkable antifungal activity against (), affording EC values ranging from 2.11-7.
View Article and Find Full Text PDFSci Signal
September 2025
Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
Replication of HIV-1 requires the coordinated action of host and viral transcription factors, most critically the viral transactivator Tat and the host nuclear factor κB (NF-κB). This activity is disrupted in infected cells that are cultured with extracellular vesicles (EVs) present in human semen, suggesting that they contain factors that could inform the development of new therapeutics. Here, we explored the contents of semen-derived EVs (SEVs) from uninfected donors and individuals with HIV-1 and identified host proteins that interacted with HIV Tat and the NF-κB subunit p65.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
Objectives: Antibiotic resistance towards penicillin has been attempted to counter by chemically modifying ampicillin through the conjugation with silver nanoparticles (AgNPs). The current study optimizes the conditions for synthesizing and characterizing AgNP-ampicillin to quantify the conjugation extent, evaluate the antibacterial efficacy, and explore the underlying antibacterial mechanisms.
Materials And Methods: AgNPs were synthesized from silver nitrate by chemical reduction method, silica-coated with tetraethyl orthosilicate (TEOS) and amine functionalized by (3-aminopropyl) triethoxysilane (APTES), which was then conjugated with ampicillin via the carbodiimide chemistry.
Introduction: Congenital Hypogonadotropic Hypogonadism (CHH) arises from defects in the synthesis, secretion, or action of gonadotropin-releasing hormone (GnRH), resulting in incomplete or absent pubertal development and various non-reproductive features. CHH is genetically heterogeneous, with over 50 genes implicated in its pathogenesis. This study aimed to elucidate the genetic variants of CHH in a cohort of patients from a single-center endocrinology unit.
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