吡啶查尔酮衍生物的合成及抑制耐甲氧西林金黄色葡萄球菌活性评价

发布时间：2018-04-18 18:59

本文选题：吡啶查尔酮 + 耐甲氧西林金黄色葡萄球菌　；参考：《有机化学》2017年04期

【摘要】：合成了一系列13个吡啶查尔酮衍生物,目标化合物的结构通过~1H NMR、~(13)C NMR和HRMS进行了确证.体外抗菌活性评价结果显示,其中的五个化合物对于革兰氏阳性金黄色葡萄球菌(ATCC 29213)表现出良好的抑制活性.为进一步评估活性,选取11株无重复的耐甲氧西林金黄色葡萄球菌(MRSA)临床株对上述5个化合物进行进一步的药效测评.数据显示,其中四个化合物对于MRSA表现出较好的抑菌活性,其中(E)-2-溴-N-{4-[3-(2-吡啶基)丙烯酰基]苯基}乙酰胺(5k)对MRSA的抑菌效力最为明显,其最小抑菌浓度(MIC)为4μg/m L.在安全性评价方面,对化合物5k进行红细胞毒性评价,结果显示化合物5k即使在1000μg/m L的浓度下对于红细胞也几乎不存在毒性.综合上述数据分析,吡啶查尔酮5k作为新型抗MRSA药物具有进一步研究的价值.
[Abstract]:A series of 13 pyridine chalcone derivatives were synthesized and the structures of the target compounds were confirmed by NMR and HRMS.The results of in vitro antibacterial activity evaluation showed that five of them showed good inhibitory activity against Gram-positive Staphylococcus aureus ATCC29213.To further evaluate the activity, 11 clinical strains of methicillin-resistant Staphylococcus aureus MRSAA were selected to further evaluate the efficacy of these five compounds.The data showed that four of the compounds showed good antibacterial activity against MRSA, and the inhibitory activity of Ela-2-bromo-N- {4- [3-pyridyl) acryloyl] phenyl} acetamide on MRSA was the most obvious, and its minimum inhibitory concentration was 4 渭 g / m 路L ~ (-1).In the aspect of safety evaluation, the erythrocyte toxicity of compound 5k was evaluated. The results showed that the toxicity of compound 5k to erythrocyte was almost non-existent even at the concentration of 1000 渭 g / mL.Based on the above data analysis, pyridine chalcone 5 k as a novel anti-MRSA drug has the value of further study.
【作者单位】：郑州大学药学院药物研究院;新药创制与药物安全性评价河南省协同创新中心;
【基金】：国家自然科学基金(Nos.U1204206,81501782) 河南省教育厅(No.17A350004)资助项目~~
【分类号】：R914.5;R96

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