N-芳基-α-氧代苯乙酰胺类化合物的设计、合成及抗增殖活性Design,synthesis and antiproliferative activity of N-aryl-α-oxophenyl-acetamides
王志伟,齐欢,吴英良,宋宏锐,贾云宏,张为革
WANG Zhi-wei1,2,QI Huan3,WU Ying-liang3,SONG Hong-rui2,JIA Yun-hong1*
摘要(Abstract)：
目的合成系列新型N-芳基-α-氧代苯乙酰胺类化合物,测定体外抗增殖活性。方法引入分子对接研究讨论该类化合物在微管蛋白秋水仙碱位点的结合方式;以3,4,5-三甲氧基苯甲醛为原料,经二氯卡宾插入反应完成中间体3,4,5-三甲氧基α-羟基苯乙酸的制备,再经酰胺化、脱苄基、PCC氧化等步骤制得目标化合物;以阿霉素为阳性对照药,采用MTT法测定目标化合物对肿瘤细胞株HT-1080和KB的抗增殖活性。结果与结论合成了20个未见文献报道的化合物,其结构经MS、1H-NMR确证;活性测试结果表明,6个化合物表现出较好的抗增殖活性。
Objective To design and synthesize N-aryl-α-oxophenyl-acetamides and eveluate their in vitro antiproliferative activity.Methods Docking simulation was performed to insert compounds 1-20 into colchicine binding site of tubulin to determine the probable binding model.The synthesis was carried out from an dichlorocarbene inserting reaction with 3,4,5-trimethoxybenzaldehyde as starting materials,as a result,an important intermediate 3,4,5-trimethoxy-α-hydroxyphenylacetic acid was prepared;then the final products were obtained followed by amidation,debenzylation,PCC oxidation.Their antiproliferative activity against HT-1080 and KB was tested by MTT assay,with ADM as the positive control.Results and Conclusions Twenty compounds which had not been reported in literatures were synthesized,and their structures were confirmed by 1H-NMR and MS.Among them,six compounds displayed promising activity.
关键词(KeyWords)：
合成;N-芳基-α-氧代苯乙酰胺类化合物;增殖抑制
synthesis;N-aryl-α-oxophenyl-acetamides;antiproliferative activity
基金项目(Foundation):
作者(Author):
王志伟,齐欢,吴英良,宋宏锐,贾云宏,张为革
WANG Zhi-wei1,2,QI Huan3,WU Ying-liang3,SONG Hong-rui2,JIA Yun-hong1*
DOI: 10.14066/j.cnki.cn21-1349/r.2013.08.010
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