苯并噻唑希夫碱类化合物的合成及其与β-淀粉样蛋白结合性能的研究  

Synthesis of benzothiazole derivatives and their binding characteristics with β-amyloid

作　　者：周琳[1] 甘昌胜[1] 汪昊曙[1] 赵珍珍[1] 潘见[1] 

机构地区：[1]合肥工业大学农产品生物化工教育部工程研究中心,安徽合肥230009

出　　处：《药学学报》2012年第5期685-688,共4页Acta Pharmaceutica Sinica

基　　金：中国科学院脑功能和脑疾病重点实验室开放基金资助项目(2009DP1731842011-2);国家高技术研究发展计划(863计划)课题资助项目(2006AA02A408)

摘　　要：阿尔茨海默病（Alzheimer’s disease,AD）是一种神经退行性疾病。随着人口老龄化,发病率逐年增高,不仅严重危害着老年人的健康,而且给家庭、社会带来了巨大的经济和人力负担。在我国1.3亿老年人中,痴呆患者600～700万人,发病率在5%以上,约占世界总病例的1/4,成为世界老年痴呆症第一大国[1]。AD常隐匿起病,逐渐出现记忆力减退。Alzheimer＇s disease（AD） is a progressive neurodegenerative disease endangering human health seriously.Recent reports have revealed that β-amyloid aggregates play a key role in the pathogenesis of AD.Thus,targeting the Aβ plaques benzothiazole derivatives were synthesized with the scaffold of the most promising imaging agent PIB（-6-OH-BTA-1,-2-（4-（methylamino）phenyl）-6-hydroxybenzothiazole） and C=N as linker to study the binding characteristics with the target protein through surface plasmon resonance（SPR） technique.These derivatives were synthesized through simple yet effective method with high yields and characterized by 1H NMR and FTIR.The binding properties（KD） were determined with Biacore X-100 instrument according to the fitting-plot curve.Compounds 3a and 3f showed high binding affinity for Aβ1-40.The results suggest that benzothiazole derivatives could be served as a scaffold to develop novel β-amyloid imaging agents for the diagnosis of AD.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 PIB 希夫碱 表面等离子共振 

分 类 号：R917[医药卫生—药物分析学] R916[医药卫生—药学]