Small molecule modulators of copper-induced Abeta aggregation.
Small molecule modulators of copper-induced Abeta aggregation.
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DOI：
10.1021/ja907045h
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发表时间：
2009-11-25
影响因子：
15
通讯作者：
Lim, Mi Hee
中科院分区：
文献类型：
--
作者：
Hindo, Sarmad S.;Mancino, Allana M.;Braymer, Joseph J.;Liu, Yihong;Vivekanandan, Subramanian;Ramamoorthy, Ayyalusamy;Lim, Mi Hee
我们设计的双功能金属螯合剂作为阿尔茨海默病(AD)的化学探针和潜在的治疗药物，是基于将金属结合部分结合到Aβ聚集体显像剂的结构框架中。利用该策略合成了两个化合物2-[4-(dimethylamino)phenyl]imidazo[1，2-a]pyridine-8-ol(1)和N1，N1-dimethyl-N4-(pyridin-2-ylmethylene)benzene-1，4-diamine(2)，并对其结构进行了表征。用光谱方法验证了化合物1和2对金属络合和A-β相互作用的双官能度。此外，还考察了1和2与CuII结合的Aβ聚集体的反应性。1和2对CuII触发的Aβ聚集的调节作用比已知的金属络合剂CQ、EDTA和Phen更有效。这些研究提出了一类新的多功能分子，用于开发解开AD中金属相关事件的化学工具，以及用于金属离子螯合治疗的潜在治疗剂。
Our design of bifunctional metal chelators as chemical probes and potential therapeutics for Alzheimer’s disease (AD) is based on the incorporation of a metal binding moiety into structural frameworks of Aβ aggregate-imaging agents. Using this strategy, two compounds 2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyridine-8-ol (1) andN1,N1-dimethyl-N4-(pyridin-2-ylmethylene)benzene-1,4-diamine (2) were prepared and characterized. The bifunctionality for metal chelation and Aβ interaction of1and2was verified by spectroscopic methods. Furthermore, the reactivity of1and2with CuII-associated Aβ aggregates was investigated. The modulation of CuII-triggered Aβ aggregation by1and2was found to be more effective than that by the known metal chelating agents CQ, EDTA, and phen. These studies suggest a new class of multifunctional molecules for the development of chemical tools to unravel metal-associated events in AD and potential therapeutic agents for metal-ion chelation therapy.
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