YM0501手性异构体抗α1受体亚型的选择活性及其构效关系  

α1-Adrenoceptor-selective antagonistic analysis and structure-activity relationship research of YM0501 enantiomers

作　　者：许芳 徐静仪 何雪兰 朱着 黎枭 袁牧 XU Fang, XU Jingyi, HE Xuelan, ZHU Zhuo, LI Xiao, YUAN Mu(School of Pharmaceutical Science, Guangzhou Medical University, Guangzhou, Guangdong, 511436 P.R. Chin)

机构地区：[1]广州医科大学药学院

出　　处：《华西药学杂志》2018年第2期119-122,共4页West China Journal of Pharmaceutical Sciences

基　　金：广东省自然科学基金项目(编号:2015A030313464);高等学校博士学科点专项科研基金联合资助(编号:20123321120007)

摘　　要：目的 研究YM0501手性异构体对α_1受体亚型选择拮抗活性及其构效关系。方法 采用双报告基因法研究YM0501手性异构体对α_1受体亚型选择拮抗活性,采用分子对接研究手性异构体分别与α_1受体亚型蛋白进行分子对接,研究作用的结构和活性关系。结果 B-YM0501对α_1受体各亚型受体亲和力：α_（1A）相当于α_（1B）的4.07倍,α_（1D）相当于α_（1B）的4.57倍。分子对接发现α_（1A）受体活性结合口袋中的TYR316和ASP113氨基酸残基与B-YM0501形成非共价键作用。结论 B-YM0501比A-YM0501或消旋体YM0501对α_（1A/D）受体的选择性更好,相对于当前临床上使用消旋体治疗良性前列腺增生,使用手性B-YM0501可能药效更好、不良反应更少。OBJECTIVE To study the antagonistic activity and structure - activity relationship of chiral isomers of YM0501 against α1 - adrenoceptor. METHODS Dual - lueiferase reporter gene assay was adopted to investigate the α1 - adrenoeeptor selective antagonistic activity of YM0501 enantiomers and molecular docking was adopted to discover structure - activity relationship. RESULTS B - YM0501 showed high binding selectivity toward α1A -- adrenoceptor and α1 - adrenoeeptor with 4.07 and 4.57 fold towards α1B- adrenoceptor respectively. Binding selectivity toward α1- adrenoceptor structure - selectivity relationship analysis suggested that some amino residues around the binding pocket of α1 - adrenoceptor. CONCLUSION B - YM0501 may exhibit higher efficacy for treating benign prostatic hyperplasia in clinic than that of raeemie YM0501.

关 键 词：YM0501 手性异构体 Α1-肾上腺素受体 亚型选择性 分子对接 

分 类 号：R96[医药卫生—药理学]