title: Pyrroloquinoxaline hydrazones as fluorescent probes for amyloid fibrils.
abstract: Here we describe the identification and preliminary characterization of a new class of pyrrolo(imidazo)quinoxaline hydrazones as florescent probes for Aβ(1-42) 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.
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), University of Siena, via Aldo Moro, 53100, Siena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.forename: Laura
authors.initials: L
authors.lastname: Colombo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Luisa
authors.initials: L
authors.lastname: Savini
authors.forename: Claudia
authors.initials: C
authors.lastname: Fracasso
authors.forename: Silvio
authors.initials: S
authors.lastname: Caccia
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Joshi
authors.forename: Pierangela
authors.initials: P
authors.lastname: Tripaldi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Isabella
authors.initials: I
authors.lastname: Fiorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
mesh_terms: D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000378:metabolism; D018360:Crystallography, X-Ray; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D006835:Hydrazones / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D015394:Molecular Structure; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011810:Quinoxalines / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D006835:Hydrazones; D010446:Peptide Fragments; D011810:Quinoxalines; C075222:amyloid beta-protein (1-42)