苯并二氢呋喃新化合物的合成与 HIV-1整合酶分子对接研究

摘要

Objective With the HIV-1 integrase enzyme molecular docking analysis synthetic dihydrobenzo-furan compounds (3)and the integrase binding mode and inhibition.Methods From vanillin and malonic acid as raw material,the Knoevenagel condensation,esterification,oxidation coupling reaction,synthesis of dihydro-benzofuran new compounds (3)2-(4-hydroxy-3-methoxy)phenyl-7-methoxy-5-[3-(2-methoxy-2-oxoethoxy)-3-oxopropenyl ]-2,3-dihydrobenzofuran-3-carboxylic acid methoxycarbonyl methyl ester. Using the computer software of Autodock compound (3)by molecular docking,prediction and analysis of the compounds have inhibition of HIV-1 integrase.Results The yield of the synthetic target compound (3)was 21.4%,which was determined by the structural identification data (3),Molecular docking showed that the compounds by docking analysis to HIV integrase (PDB:1QS4)indicates that the amino acids resi-due of asparagine,glutamine and histidine interact with the enzyme through hydrogen bond,π-π coinci-dence and hydrophobic force.Conclusion The synthesis route of the oxidative coupling reaction is short, the reaction condition is mild,the operation is simple and easy to control,the target compound is obtained by column chromatography,docking displayed that compounds inhibited the HIV-1 integration enzyme.%目的：通过与 HIV-1整合酶的分子对接，分析合成的苯并二氢呋喃类化合物（3）与整合酶的结合方式和抑制作用。方法以香草醛和丙二酸为原料，经 Knoevenagel 缩合、酯化、氧化偶联反应，合成苯并二氢呋喃新化合物（3）2-（4-羟基-3-甲氧基）苯基-7-甲氧基-5-[3-（2-甲氧基-2-氧代乙氧基）-3-氧代丙烯基]-2，3-二氢苯并呋喃-3-羧酸甲氧羰基甲酯，采用计算机 Autodock 软件对化合物（3）进行分子对接，预测分析该化合物是否有抑制 HIV-1整合酶的作用。结果合成目标化合物（3）的产率为21．4％，经结构鉴定数据确定为化合物（3），分子对接显示化合物（3）和 HIV-1整合酶（PDB：1QS4）中的天冬酰胺、谷氨酰胺、组氨酸等氨基酸残基之间存在氢键、π-π共轭叠合作用和疏水作用。结论氧化偶联反应的合成路线较短，反应条件温和，操作简单易控，经柱层析分离获得目标化合物，分子对接显示化合物（3）对 HIV-1整合酶有抑制的作用。