Homoisoflavonoids as potential imaging agents for 尾-amyloid plaques in Alzheimer's disease

详细信息    查看全文

• 作者：Changsheng Gan^a ; ^{gancs7894@163.com" class="auth_mail} ; Zhenzhen Zhao^a ; Dou-Dou Nan^b ; Binbin Yin^a ; Jingyi Hu^a
• 关键词：Alzheimer's disease ; Amyloid ; Imaging agent ; Homoisoflavonoid ; Binding assay
• 刊名：European Journal of Medicinal Chemistry
• 出版年：9 April, 2014
• 年：2014
• 卷：76
• 期：Complete
• 页码：125-131
• 全文大小：532 K

文摘

A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones, 3a-l] as novel potential diagnostic imaging agents targeting 尾-amyloid (A尾) plaques in Alzheimer's disease (AD) were synthesized and evaluated. In聽vitro binding studies using A尾_1-40 aggregates with [¹²⁵I]IMPY as the reference ligand showed that these compounds demonstrated high to low binding affinities at the K_i values ranged from 9.10 to 432.03聽nM, depending on the substitution of the phenyl ring. Fluorescent staining in聽vitro indicated that one compound with a N,N-dimethylamino group intensely stained A尾 plaques within brain sections of postmortem AD patients. Biodistribution studies in normal mice after i.v. injection of the radioiodinated homoisoflavonoid displayed good initial brain uptake (2.61% ID/g at 2聽min postinjection) and rapid clearance from the brain (0.18% ID/g at 60聽min), which is desirable for amyloid imaging agents. The results strongly suggest that these derivatives are worthy of further study and may be useful amyloid imaging agents for early detection of amyloid plaques in the brain of AD.