A multifunctional metal regulator as the potential theranostic agent: Design, synthesis, anti-AD activities and metallic ion sensing properties

Abstract

Although there is no cure for Alzheimer's disease (AD) due to its complex pathogenesis, early detection and treatment can help delay the development of the disease. So, it is necessary to develop multifunctional metal regulators that can integrate the therapeutics and diagnostics effect against AD. In this work, N-(anthracene-9-ylmethylene)benzohydrazide (probe 1), a fluorescent probe with imine and carbonyl as chelating sites was designed and synthesized. Results showed that 1 had good activities related to AD, such as regulation of metal homeostasis, inhibition of β-amyloid (Aβ) aggregation and scavenging of reactive oxygen species. The selectivity experiment showed that probe 1 had a good recognition effect on Cu²⁺. Fluorescence imaging assay also indicated that probe 1 had a good fluorescence imaging effect on Cu²⁺ in living cells. Furthermore, probe 1 had showed no cytotoxicity and good BBB permeability. These results indicated that probe 1 had potential diagnostic and therapeutic capabilities, and can be used as the multifunctional theranostic agent for AD.

Keywords: Alzheimer's disease; Fluorescence sensor; Metal dyshomeostasis; Theranostic agent.