Design and Enzyme‐Targeted Assessment of 1,2,4‐Triazole–1,8‐Naphthalimide Hybrids in Drug Discovery.

This study reports the design, synthesis, and biological evaluation of novel hybrid 1,2,4‐triazole–1,8‐naphthalimide derivatives using both classical and environmentally friendly synthetic routes. The synthetic strategy involved a multistep process starting with the preparation of triazolylthioaceti...

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Publicado en:BioMed Research International Vol. 2025; pp. 1 - 26
Autores principales: Korol, Nataliya, Slyvka, Mykhailo, Rusyn, Ivan, Pallah, Oleksandra, Burmei, Svitlana, Bestritska, Viktoriia, Supuran, Claudiu T.
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 8/11/2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/11/2025
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      pub: Wiley-Blackwell
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        10.1155/bmri/6115993
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        atl: Design and Enzyme‐Targeted Assessment of 1,2,4‐Triazole–1,8‐Naphthalimide Hybrids in Drug Discovery.
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          Korol, Nataliya
          Slyvka, Mykhailo
          Rusyn, Ivan
          Pallah, Oleksandra
          Burmei, Svitlana
          Bestritska, Viktoriia
          Supuran, Claudiu T.
        affil: Department of Organic Chemistry,, Educational and Research Institute of Chemistry and Ecology,, Uzhhorod National University,, Uzhhorod, Ukraine
      sug:
        subj:
          Heterocyclic Compounds Antagonists and Inhibitors
          Piperidines Analogs and Derivatives
          Drug Discovery
          Drug Design
          Antiinfective Agents Pharmacodynamics
          Antiinflammatory Agents Pharmacodynamics
          Molecular Docking Simulation
          Biochemical Phenomena
          Biological Phenomena
          Human
          Funding Source
          Molecular Structure
          Bromine
          Bioinformatics
          Interleukins
          Heterocyclic Compounds Metabolism
          Cyclization
          Conservation of Natural Resources
          Lactobacillus
      ab: This study reports the design, synthesis, and biological evaluation of novel hybrid 1,2,4‐triazole–1,8‐naphthalimide derivatives using both classical and environmentally friendly synthetic routes. The synthetic strategy involved a multistep process starting with the preparation of triazolylthioacetic acid esters, followed by electrophilic cyclization—employing both conventional bromine and a green, bromine‐free method—and culminating in amidation reactions to yield the target compounds. Structural modifications, including the incorporation of pyridinyl and benzoate moieties, were introduced to enhance biological activity. The compounds were evaluated for antimicrobial and anti‐inflammatory activities. In antimicrobial assays, several derivatives demonstrated selective activity, with Compound 5f showing the strongest broad‐spectrum antibacterial effects, particularly against Bacillus cereus and Lactobacillus plantarum, and Compound 3e displaying notable dual‐action activity against both bacterial and fungal strains. These observations underscore the influence of specific functional groups on microbial targeting and membrane penetration. Anti‐inflammatory potential was assessed via IL‐6 inhibition using ELISA. Significant reductions in IL‐6 levels were observed for Compounds 3a, 3c, 3e, 4, 5c, 5f, and 5g, indicating promising activity, with Compounds 5c and 3a reducing IL‐6 levels to 7 pg/mL. The complementary molecular docking studies revealed strong binding affinities for Compound 5f across multiple bacterial enzymes, suggesting effective interactions through hydrogen bonding, electrostatic, and hydrophobic forces and supporting its potential to target iron‐regulated pathways and fosfomycin resistance mechanisms. Overall, the integrative approach combining synthetic chemistry, biological assays, and computational modeling highlights the potential of these hybrid 1,2,4‐triazole derivatives as candidates for further development as antimicrobial and anti‐inflammatory agents.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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