1,2,4-三唑-1,8-萘酰亚胺化合物的设计与酶标评价

IF 2.3 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
BioMed Research International Pub Date : 2025-08-10 eCollection Date: 2025-01-01 DOI:10.1155/bmri/6115993
Nataliya Korol, Mykhailo Slyvka, Ivan Rusyn, Oleksandra Pallah, Svitlana Burmei, Viktoriia Bestritska
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引用次数: 0

摘要

本研究报道了新型杂化1,2,4-三唑-1,8-萘酰亚胺衍生物的设计、合成和生物学评价。合成策略包括一个多步骤的过程,从制备三唑硫乙酸酯开始,然后是亲电环化-使用传统的溴和绿色的无溴方法-最终在酰胺化反应中产生目标化合物。结构修饰,包括吡啶基和苯甲酯部分的掺入,被引入以提高生物活性。化合物的抗菌和抗炎活性进行了评价。在抗菌试验中,几种衍生物显示出选择性活性,其中化合物5f表现出最强的广谱抗菌作用,特别是对蜡样芽孢杆菌和植物乳杆菌,化合物3e对细菌和真菌菌株均表现出显著的双作用活性。这些观察结果强调了特定官能团对微生物靶向和膜渗透的影响。ELISA法检测IL-6抑制作用。化合物3a、3c、3e、4、5c、5f和5g显著降低IL-6水平,表明有良好的活性,化合物5c和3a将IL-6水平降低至7 pg/mL。互补的分子对接研究显示,化合物5f与多种细菌酶具有很强的结合亲和性,表明化合物5f通过氢键、静电和疏水力进行有效的相互作用,并支持其靶向铁调控途径和磷霉素耐药机制的潜力。总的来说,结合合成化学,生物测定和计算建模的综合方法突出了这些杂化1,2,4-三唑衍生物作为抗菌和抗炎药物进一步开发的候选药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.

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来源期刊
BioMed Research International
BioMed Research International BIOTECHNOLOGY & APPLIED MICROBIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
6.70
自引率
0.00%
发文量
1942
审稿时长
19 weeks
期刊介绍: BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject areas.
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