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N-{[(硫色满-4-酮-3-基)-苯基]-甲基}乙酰胺类化合物的合成、α-葡萄糖苷酶抑制活性评价及分子对接研究 被引量:1

Synthesis, biological activity and molecular docking research of N-{[(4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide derivatives as α-glucosidase inhibitors
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摘要 利用Dakin-West反应"一锅法"合成了12个N-{[(硫色满-4-酮-3-基)-苯基]-甲基}乙酰胺衍生物。所合成的化合物经^1H NMR、^13C NMR、IR和HR-MS等方法进行了结构表征。葡萄糖氧化酶法测试结果表明,大多数目标分子表现出α-葡萄糖苷酶抑制活性,其中化合物4k抑制作用最强(在浓度为5.39 mmol·L^-1时,绝对抑制活性达到87.3%)。根据活性测试结果对合成化合物的构效关系进行了讨论。用分子对接方法研究了化合物4k与α-葡萄糖苷酶的作用模式,为进一步的研究提供了依据。 In order to develop potent antidiabetic agents that have inhibitory effect to α-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by ^1H NMR, ^13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-4l were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol·L^-1. The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
作者 周冠 梁国超 韩晓燕 钟一凡 董芸芳 罗晓聪 金宏威 宋亚丽 ZHOU Guan, LIANG Guo-chao, HAN Xiao-yan, ZHONG Yi-fan, DONG Yun-fang, LUO Xiao-cong, JIN Hong-wei, SONG Ya-li (1, College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, China; 2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China; 3. Yung Shin Pharm. lnd. (Kunshan) Co., Ltd., Suzhou 215300, China; 4. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China )
出处 《药学学报》 CAS CSCD 北大核心 2016年第1期93-99,共7页 Acta Pharmaceutica Sinica
基金 河北大学自然科学基金资助项目(2010-194) 河北省药物质量分析控制重点实验室开放基金资助课题
关键词 硫色满酮 Α-葡萄糖苷酶抑制剂 一锅法 β-乙酰氨基酮 thiochromanone α-glucosidase inhibitor one-pot synthesis β-acetamido ketone
作者简介 通讯作者Tel,Fax:86—312—5971107,E—mail:yalisong@hbu.edu.cn
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