| 基于UDP-半乳糖变异酶靶标的肉桂酰氨基酸衍生物的合成及生物活性 |
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| 引用本文： | 王青青,傅建,何梓瑶,娄华勇,潘卫东,张永萍,吴静澜.基于UDP-半乳糖变异酶靶标的肉桂酰氨基酸衍生物的合成及生物活性[J].化学通报,2023,86(2):216-221. |
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| 作者姓名： | 王青青 傅建 何梓瑶 娄华勇 潘卫东 张永萍 吴静澜 |
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| 作者单位： | 贵州中医药大学,贵州中医药大学,贵州中医药大学药学院,贵州医科大学药学院/省部共建药用植物功效与利用国家重点实验室,贵州医科大学药学院/省部共建药用植物功效与利用国家重点实验室,贵州中医药大学,贵州中医药大学 |
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| 基金项目： | 国家自然科学基金项目(81903517、32060100)、贵州省科技计划项目(黔科合基础[2020]1Y371、黔科合支撑[2021]一般411、黔科合平台人才[2017]5701)、贵阳市高层次创新型青年科技人才(筑科合同[2021]43-10号),贵州省(第六批)高层次创新型人才遴选培养计划(“千”层次)项目资助 |
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| 摘 要： | 为改善前期发现的UDP-半乳糖变异酶(UGM)抑制剂迷迭香酸的稳定性，通过生物电子等排策略，引入稳定性较好的酰胺键来重新构建该化合物。本文设计合成了8个新的肉桂酰氨基酸衍生物，并进行酶水平和菌株水平的活性评价。酶活性测定结果表明，化合物5a～5h对UGM具有不同程度的抑制活性，其中化合物5e、5g和5h表现出显著的抑制活性，Kd值均达到了微摩尔级，与目前文献报道的最好抑制剂活性相当。化合物5e对UGM的亲和力比母体化合物迷迭香酸提高了17倍，Kd分别为4±2μmol/L(KpUGM)和38±5μmol/L(MtUGM)。5e和5h体外对牛型结核分枝杆菌的MIC分别为50和100μg/mL。结果表明，目标化合物对UGM具有较强的抑制作用，值得进一步的结构修饰，其也可为开发具有较好前景的抗结核候选药物提供参考。
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| 关 键 词： | UDP-半乳糖变异酶 肉桂酰氨基酸衍生物 抗结核 分子对接 |
| 收稿时间： | 2022/6/30 0:00:00 |
| 修稿时间： | 2022/7/25 0:00:00 |
Synthesis and Biological Evaluation of Cinnamoyl Amide Derivatives as UDP-galactopyranose Mutase Inhibitors |
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| Qingqing Wang,Jian Fu,Ziyao He,Huayong Lou,Weidong Pan,Yongping Zhang and Jinglan Wu.Synthesis and Biological Evaluation of Cinnamoyl Amide Derivatives as UDP-galactopyranose Mutase Inhibitors[J].Chemistry,2023,86(2):216-221. |
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| Authors: | Qingqing Wang Jian Fu Ziyao He Huayong Lou Weidong Pan Yongping Zhang and Jinglan Wu |
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| Institution: | College of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Miao Medicine Engineering Technology Research Center/Guizhou Traditional Chinese Medicine Processing and Preparation Engineering Technology Research Center,Guiyang,College of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Miao Medicine Engineering Technology Research Center/Guizhou Traditional Chinese Medicine Processing and Preparation Engineering Technology Research Center,Guiyang,College of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Miao Medicine Engineering Technology Research Center/Guizhou Traditional Chinese Medicine Processing and Preparation Engineering Technology Research Center,Guiyang,The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang,The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang,College of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Miao Medicine Engineering Technology Research Center/Guizhou Traditional Chinese Medicine Processing and Preparation Engineering Technology Research Center,Guiyang,College of Pharmacy,Guizhou University of Traditional Chinese Medicine/National Miao Medicine Engineering Technology Research Center/Guizhou Traditional Chinese Medicine Processing and Preparation Engineering Technology Research Center,Guiyang |
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| Abstract: | |
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| Keywords: | UDP-galactopyranose mutase Cinnamoyl amid derivatives Antituberculosis Molecular modeling |
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