【摘 要】
：
M3受体是人体内分布广泛的一种重要的毒蕈碱乙酰胆碱受体亚型,与膀胱过度活动症、心律失常、呼吸道及支气管疾病密切相关.设计与合成M3受体拮抗剂对于开发治疗相关疾病的药物
【机 构】
：
青岛科技大学化工学院,山东药品食品职业学院,华东理工大学药学院,
论文部分内容阅读
M3受体是人体内分布广泛的一种重要的毒蕈碱乙酰胆碱受体亚型,与膀胱过度活动症、心律失常、呼吸道及支气管疾病密切相关.设计与合成M3受体拮抗剂对于开发治疗相关疾病的药物具有重要理论意义和应用价值。本文采用同源模建方法,构建了人M3受体蛋白的三维结构,基于M3受体拮抗剂的结构构建了其药效团模型,其中较理想的模型含有6个药效团特征元素。利用药效团模型进行了虚拟筛选,虚拟筛选的数据库是本实验室构建的虚拟化合物库,发现了10个新型的对M3受体有拮抗作用的化合物。最后对这10个化合物进行了分子对接,根据对接结果,发现3个化合物对接能量及结合方式比较合理,为M3受体拮抗剂的合成研究及活性测定奠定了基础。
M3 receptor is an important muscarinic acetylcholine receptor subtype widely distributed in the human body and is closely related to overactive bladder, arrhythmia, respiratory and bronchial diseases.Design and synthesis of M3 receptor antagonists for the development of treatment-related Diseases of the drug has important theoretical significance and application value. In this paper, the three-dimensional structure of human M3 receptor protein was constructed by homology modeling method. Based on the structure of M3 receptor antagonist, its pharmacophore model was constructed. The ideal model contains six pharmacophore characteristic elements. The pharmacophore model was used for virtual screening. The virtual screening database was a virtual compound library constructed by our laboratory, and 10 new compounds that antagonized the M3 receptors were found. Finally, the molecular docking of these 10 compounds was carried out. According to the docking results, it was found that the docking energies and binding modes of the three compounds were reasonable, which laid the foundation for the synthesis and activity determination of M3 receptor antagonists.
其他文献
The effects and heat transfer mode of water film and sprinkler system on the heat-resistant property associated with the insulation of a fireproof glass were in
Functional gene markers can provide important information about functional gene diversity and potential activity of microbial communities.Although microarray te
The properties and mechanism of concrete under water leakage corrosion were studied in terms of the dissolution of calcium oxide and silicon oxide from concrete
The pH dependent sorption of rare earth ions (La(Ⅲ), Ce(Ⅲ), Pr(Ⅲ), Nd(Ⅲ), Y(Ⅲ), Sm(Ⅲ), Eu(Ⅲ), Gd(Ⅲ), Tb(Ⅲ), Dy(Ⅲ), Ho(Ⅲ), Er(Ⅲ), Lu(Ⅲ), and Yb(Ⅲ))
The possibilities of MSWI fly ash as a major constituent of novel solidification/stabilization matrices for secure landfill were investigated by mixing MSWl fly
The oxidation behavior of a cast polycrystalline Co-base superalloy was studied at temperatures from 900 to 1050℃ and analyzed by thermogravimetric analysis (T
The comparative study on adsorptions of Pb(Ⅱ) and Cr(Ⅵ) ions by free cells and immobilized cells of Synechococcus sp.was performed,in which different aspects
A Gram-negative,facultative autotrophic bacterium strain PJH was isolated from the acidic mine drainages sampled in Dexing Mine,Jiangxi Province,China.The isola
Three novel β-diketones (HPPP, HTPP, and HFPP) ligands were synthesized by Sonogashira coupling reaction and Claisen con-densation. The structure of β-diketon
The bioleaching of chalcopyrite in shake flasks was investigated by using pure Acidithiobacillus ferrooxidans and mixed culture isolated from the acid mine drai