| 9-取代巴马汀衍生物抗幽门螺杆菌活性研究 |
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| 引用本文： | 范田运,庞晶,曾庆轩,汪燕翔,游雪甫,宋丹青. 9-取代巴马汀衍生物抗幽门螺杆菌活性研究[J]. 药学学报, 2020, 0(6): 1237-1244 |
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| 作者姓名： | 范田运 庞晶 曾庆轩 汪燕翔 游雪甫 宋丹青 |
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| 作者单位： | 中国医学科学院、北京协和医学院医药生物技术研究所、北京市抗感染重点实验室;中国医学科学院/北京协和医学院药物研究所 |
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| 基金项目： | 中国医学科学院医学与健康科技创新工程(2019-12M-1-005,2017-I2M-1-012);北京市自然科学基金资助项目(7172136);国家自然科学基金资助项目(81603195)。 |
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| 摘 要： | 本研究共设计合成了15个9-取代巴马汀(palmatine,1,异喹啉生物碱类)衍生物,首次评价了其体外抗幽门螺杆菌(Helicobacter pylori,Hp)活性。初步构效关系表明9-位引入适当的二级胺取代基利于抗菌活性提高。其中,代表性化合物5a对部分甲硝唑耐药菌株显示较好活性,最低抑菌浓度(MICs)值为4μg·mL-1,优于先导物1。另外,5a显示良好安全性,口服LD50>1 000 mg·kg-1。分子对接实验结果提示,化合物5a可能通过作用于Hp脲酶而发挥抑菌作用。本研究结果为巴马汀类衍生物发展成一类新颖抗Hp联合用药组分提供了重要科学数据。
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| 关 键 词： | 9-取代巴马汀 幽门螺杆菌 构效关系 分子对接 |
Anti-Helicobacter pylori activities of 9-substituted palmatine derivatives |
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| FAN Tian-yun,PANG Jing,ZENG Qing-xuan,WANG Yan-xiang,YOU Xue-fu,SONG Dan-qing. Anti-Helicobacter pylori activities of 9-substituted palmatine derivatives[J]. Acta pharmaceutica Sinica, 2020, 0(6): 1237-1244 |
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| Authors: | FAN Tian-yun PANG Jing ZENG Qing-xuan WANG Yan-xiang YOU Xue-fu SONG Dan-qing |
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| Affiliation: | (Beijing Key Laboratory of Antimicrobial Agents,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China) |
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| Abstract: | Fifteen 9-substituted palmatine(1)derivatives were synthesized and evaluated for their anti-Helico‐bacter pylori(Hp)activities in vitro.Structure-activity relationship studies revealed that introducing appropriate substituted secondary amino group at position 9 of lead 1 might be beneficial for potency.Among them,compound5a showed the most potential activity against metronidazole(Met)resistant Hp isolates with minimal inhibitory concentrations(MICs)of 4μg·mL^-1,much better than that of lead 1.Compound 5a displayed satisfactory safety profile in acute toxicity assay.Molecular docking suggested that 5a might act on Hp urease.The results provided key scientific evidence for the development of 1 derivatives into a new class of anti-Hp component. |
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| Keywords: | 9-substitute palmatine Helicobacter pylori structure-activity relationship molecular docking |
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