Phenothiazine-based theranostic compounds for in vivo near-infared fluorescence imaging of β-amyloid plaques and inhibition of Aβ aggregation

A global burden of Alzheimer's disease (AD) has been growing over last decades. Evidence indicates that β-amyloid (Aβ) production and senile plaque deposition in the brain is causative in the onset of AD pathogenesis. It appears much earlier than cognitive decline and plays a key role in initiating and developing AD neuropathology. As such, there is an intense passion with discovering theranostic agents which make a significant impact in diagnostic and therapy. Herein, we report an investigation of novel phenothiazine-based compounds as promising potential theranostic agents for AD. Remarkably, they have exhibited a high binding affinity toward Aβ aggregates, a good biostability and a strong increase in their fluorescence intensity with blue shift when interacting with Aβ aggregates. Furthermore, they have been simultaneously applied to perform NIR in vivo imaging of β-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aβ monomer from forming toxic oligmers and to reduce Aβ-induced toxicity of human neuroblastoma cells (SH-SY5Y). [Display omitted] •New phenothiazine-based compounds were synthesized and evaluated as promising theranostic agents for AD.•The probes displayed good bio-stability, low toxicity and strong fluorescence intensity upon binding with Aβ aggregates.•The in vivo imaging showed that they had good BBB penetration and could target Aβ plaques in the brain.•These compounds could suppress Aβ aggregation and protect human neuroblastoma SH-SY5Y cells against Aβ-induced toxicity.