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| 新型香豆素酰胺类衍生物的合成及抑菌机制研究 |
| Synthesis and antibacterial mechanism study of novel coumarin amide derivatives |
| 投稿时间：2026-03-31 修订日期：2026-04-28 |
| DOI： |
| 中文关键词: 香豆素酰胺衍生物 产肠毒素大肠杆菌 抑菌活性 网络药理学 分子对接 |
| 英文关键词:Coumarin amide derivatives, Enterotoxigenic Escherichia coli, Antibacterial activity, Network pharmacology, Molecular docking[1] |
| 基金项目: |
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| 摘要点击次数: 13 |
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| 中文摘要: |
| 本文设计合成了12个香豆素酰胺类衍生物，评价其对产肠毒素大肠杆菌（ETEC）的抑菌活性并探究其作用机制。采用Perkin反应合成香豆素母核，再与不同的取代胺进行酰胺缩合，制备得到一系列结构新颖的香豆素酰胺类衍生物，结构经核磁共振和质谱确证。采用微量稀释法测定化合物对ETEC的最小抑菌浓度（MIC）和半数抑制浓度（IC50），所有目标化合物均对ETEC表现出抑菌活性，其中XA2-4活性最优，MIC为0.5±0.05 mg/mL，IC50为0.16±0.02 mg/mL，优于阳性对照利奈唑胺。网络药理学筛选得出recA、metG、pyrG等为核心靶点，分子对接显示候选化合物XA2-4与核心靶点蛋白均具有良好的结合亲和力。qPCR验证结果表明，XA2-4可显著下调recA、metG和pyrG基因的表达，其中pyrG基因对药物干预最为敏感。 |
| 英文摘要: |
| This study designed and synthesized 12 coumarin amide derivatives, evaluated their antibacterial activity against Enterotoxigenic Escherichia coli (ETEC), and explored their mechanisms of action. The coumarin core was synthesized via the Perkin reaction and then subjected to amide condensation with different substituted amines, resulting in a series of novel coumarin amide derivatives. Their structures were confirmed by nuclear magnetic resonance and mass spectrometry. The minimum inhibitory concentration(MIC) and half-inhibitory concentration(IC50) of the compounds against ETEC were determined using the microdilution method. All target compounds exhibited antibacterial activity against ETEC, with XA2-4 showing the best activity, with MIC of 0.5±0.05 mg/mL and IC50 of 0.16±0.02 mg/mL, superior to the positive control linaclotide. Network pharmacology screening identified recA, metG, pyrG and other genes as core targets. Molecular docking revealed that the candidate compound XA2-4 exhibited good binding affinity with the core target proteins. qPCR validation results indicated that XA2-4 significantly downregulated the expression of recA, metG and pyrG genes, with pyrG gene being the most sensitive to drug intervention. |
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