2-Styrylquinolines with push-pull architectures as sensors for β-amyloid aggregation with theranostic properties

Abstract

The design and synthesis of a small library of 2-styrylquinoline derivatives containing a push-pull system, in order to displace their fluorescence emission towards the NIR region, is described. We describe here their synthesis, fluorescent characterization and pharmacological evaluation against different amyloid proteins. Their study showed that these compounds are capable to change their spectroscopic properties upon protein interaction, resulting in changes in the absorption and emission wavelengths, together with increased fluorescence intensity. They also showed sensitivity to pH and environment polarity, exhibiting red shifts in lower polarity environments with regard to aqueous media. Inner charge transfer is observed and employed for detecting the interaction of these compounds with protein aggregates. The changes in the fluorescence intensity allows the calculation of the dissociation constants values protein-sensor. These spectroscopic results were the basis for the use of these compounds to selectively visualize β-amyloid plates in samples of cerebral tissue from deceased Alzheimer patients under fluorescence microscopy, using immunofluorescence techniques. Pharmacological assays showed the ability of compounds to inhibit the aggregation of the Aβ1-42 and AcPHF6 peptides, representing tau protein. They also showed neuroprotective activity following okadaic acid insult.