作者:Sandra Gemma、Laura Colombo、Gianluigi Forloni、Luisa Savini、Claudia Fracasso、Silvio Caccia、Mario Salmona、Margherita Brindisi、Bhupendra P. Joshi、Pierangela Tripaldi、Gianluca Giorgi、Orazio Taglialatela-Scafati、Ettore Novellino、Isabella Fiorini、Giuseppe Campiani、Stefania Butini
DOI:10.1039/c1ob05288h
日期:——
Here we describe the identification and preliminary characterization of a new class of pyrrolo(imidazo)quinoxaline hydrazones as flurescent probes for Aβ1-42 fibrils. All the newly developed compounds were able to bind amyloid fibrils formed in vitro and some of them displayed an increase of their fluorescence upon binding. When tested on brain tissue preparations presenting Aβ deposits, the described hydrazones selectively stained amyloid structures and did not display aspecific binding. The hydrazones did not show antifibrillogenic activity and electron microscopy analysis revealed that they do not interfere with fibrils structure. The described pyrrolo(imidazo)quinoxalines could be useful for studying amyloid structures in vitro. Moreover, their experimentally proven ability to cross the blood–brain barrier in mouse opens the possibility of developing these compounds as potential amyloid imaging agents for in vivo applications.
在此,我们介绍了一类新的吡咯(咪唑)喹喔啉肼类化合物作为 Aβ1-42 纤维的荧光探针的鉴定和初步表征。所有新开发的化合物都能与体外形成的淀粉样蛋白纤维结合,其中一些化合物在结合后荧光增强。在对出现 Aβ 沉积的脑组织制备物进行测试时,所述的酰肼类化合物可选择性地染色淀粉样蛋白结构,而不会显示出特异性结合。这些酰肼没有显示出抗纤维化活性,电子显微镜分析表明它们不会干扰纤维结构。所述吡咯(咪唑)喹喔啉类化合物可用于体外研究淀粉样蛋白结构。此外,实验证明它们能够穿过小鼠的血脑屏障,这为开发这些化合物作为体内应用的潜在淀粉样蛋白成像剂提供了可能。