The formation of amyloid-β (Aβ) plaques is one of the key neuropathological hallmarks of Alzheimer's disease (AD). Near-infrared (NIR) probes show great potential for imaging of Aβ plaques in vivo and in vitro. Dicyanoisophorone (DCIP) based Aβ probes have attracted considerable attention due to their exceptional properties. However, DCIP probes still has some drawbacks, such as short emission wavelength (<650 nm) and low fluorescence intensity after binding to Aβ. It is clear that further modification is needed to improve their luminescence efficiency and sensitivity. We designed and synthesize four novel pyrrolidine-alkylamino-substituted DCIP derivatives (-) as imaging agents for β-amyloid (Aβ) aggregates. Compound responds better to Aβ aggregates than the other three compounds (, and ) and its precursor DCIP. The calculated detection limit is to be as low as 0.23 μM. Compound shows no cytotoxicity in the tested concentration for SH-SY5Y and HL-7702 cells. Additionally, compound is successfully applied to monitor Aβ aggregates in live SH-SY5Y cells and APP/PS1 transgenic mice. The retention time in the transgenic mice brain is much longer than that of age-matched wild-type mice. The results indicates that compound had an excellent ability to penetrate the blood-brain barrier and it could effectively distinguish APP/PS1 transgenic mice and wide-type mice. This represents its promising applications for Aβ detection in basic and biomedical research.

中文翻译：

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新型吡咯烷-烷基氨基取代的二氰基异佛尔酮衍生物作为近红外荧光探针用于体外和体内β-淀粉样蛋白成像


β 淀粉样蛋白 (Aβ) 斑块的形成是阿尔茨海默病 (AD) 的关键神经病理学标志之一。近红外 (NIR) 探针在体内和体外 Aβ 斑块成像方面显示出巨大的潜力。基于二氰基异佛尔酮 (DCIP) 的 Aβ 探针由于其优异的性能而引起了广泛的关注。然而，DCIP探针仍然存在一些缺点，例如发射波长短（<650 nm）和与Aβ结合后荧光强度低。显然，需要进一步修饰以提高其发光效率和灵敏度。我们设计并合成了四种新型吡咯烷-烷基氨基取代的 DCIP 衍生物 (-) 作为 β-淀粉样蛋白 (Aβ) 聚集体的显像剂。该化合物对 Aβ 聚集体的反应比其他三种化合物 (、 和 ) 及其前体 DCIP 更好。计算出的检测限低至 0.23 μM。在测试浓度下，化合物对 SH-SY5Y 和 HL-7702 细胞没有细胞毒性。此外，该化合物还成功应用于监测活体 SH-SY5Y 细胞和 APP/PS1 转基因小鼠中的 Aβ 聚集体。转基因小鼠大脑中的保留时间比年龄匹配的野生型小鼠长得多。结果表明，该化合物具有良好的血脑屏障穿透能力，能有效区分APP/PS1转基因小鼠和宽型小鼠。这代表了其在基础和生物医学研究中 Aβ 检测的广阔应用前景。