| 摘要: |
| 【目的】制备N-苯基-β-卤代丙炔酰胺类化合物，探究其对白色念珠菌的抗菌活性、作用机制和构效关系。【方法】 通过取代苯胺和丙炔酸的缩合反应和炔氢的卤代反应，得到目标化合物及其类似物。采用微量稀释法，测定化合物对6株白色念珠菌抑菌率≥80%的最小浓度（MIC80）并分析构效关系。通过扫描电镜和荧光分析试验，探究化合物对细胞形态、活性氧水平、线粒体膜电位和细胞膜通透性的影响。【结果】 合成了23种化合物，其中包括15种新化合物和8种已知化合物。大部分化合物对6株供试菌均表现出较强的抑制活性（MIC80<10 μg/mL），其中化合物3p（3-碘-N-（3,5 二甲基苯基）丙炔酰胺）的抑菌活性最高（MIC80为0.43～1.65 μg/mL），远优于阳性药物氟康唑。构效关系分析发现，炔氢的碘代可显著增强化合物抗白色念珠菌的活性，苯环上的3位有氯、溴、碘、甲基或异丙基时，可显著增强化合物的活性，而3，5位同时存在卤素原子或甲基时，可极大增强化合物的抑菌活性。化合物3p可导致白色念珠菌细胞壁破裂和菌体皱缩，改变细胞膜的通透性，降低活性氧水平和线粒体膜电位。【结论】N-苯基-β-碘丙炔酰胺是研发抗念珠菌药物的一个新型先导骨架，化合物3p是具有开发潜力的抗白色念珠菌药物的候选-分子。 |
| 关键词: 丙炔酰胺 白色念珠菌 抗菌活性 构效关系 作用机制 |
| DOI：10.13207/j.cnki.jnwafu.2025.08.014 |
| 分类号: |
| 基金项目:国家自然科学基金项目（31872008） |
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| Synthesis and anti-Candida albicans activity of N-phenyl-β-halopropargylamide compounds and its action mechanism |
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LIU Le, WEI Peng’an, XIE Bingyi, SHE Dongmei, ZHOU Le
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College of Chemistry and Pharmcy,Northwest A&F University,Yangling,Shaanxi 712100,China
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| Abstract: |
| 【Objective】This research aimed to synthesize N-phenyl-β-halopropargylamide compounds,explore their antifungal activity,mechanism and structure-activity relationship,and find drug candidate molecules against Candida albicans.【Method】The target compounds and their analogues were obtained by condensation reaction of substituted aniline with propiolic acid followed by halogenation reaction of alkyne hydrogen.Microdilution method was used to determine the minimum concentration of the compound with a bacteriostatic rate ≥80% against Candida albicans,and scanning electron microscopy and fluorescence analysis were used to explore its effects on cell morphology,reactive oxygen species level,mitochondrial membrane potential and cell membrane permeability.【Result】23 compounds were synthesized,including 15 new compounds and 8 known compounds.Most of the compounds showed strong inhibitory activities (MIC80<10 μg/mL) against all the six strains tested,with the highest activity observed in compound 3p (MIC80 was 0.43-1.65 μg/mL),which was far superior to the positive drug fluconazole.The structure-activity relationship study showed that the iodation of alkyne hydrogen can significantly enhance the anti Candida albicans activity of the compound.When there were chlorine,bromine,iodine,methyl or isopropyl in the third position of the benzene ring,the activity of the compound was significantly enhanced.When there were halogen atoms or methyl groups in the third and fifth positions,the activity of the compound was highly significantly enhanced.Compound 3p caused cell wall rupture and cell shrinkage of Candida albicans,changed the permeability of cell membrane,and reduced the level of reactive oxygen species and mitochondrial membrane potential.【Conclusion】N-phenyl-β-iodopropionamide is a new lead skeleton for developing anti-Candida drugs,and compound 3p can be considered as a promising candidate molecule for development of anti-C.albicans drugs. |
| Key words: propargyl amide Candida albicans antibacterial activity structure-activity relationship action mechanism |
