N,N′-1,10-Bis(Naringin) Triethylenetetraamine, Synthesis and as a Cu(II) Chelator for Alzheimer’s Disease Therapy

Abstract

The bis-Schiff base of N,N′-1,10-bis(naringin) triethylenetetraamine (1) was prepared, as a copper(II) ion chelator, compound 1 was used for Alzheimer’s disease therapy in vitro. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of compound 1 showed that this Schiff base could promote PC12 cells proliferation, and also, compound 1 could inhibit Cu²⁺-amyloid-β (Aβ)_1–42 mediated cytotoxicity on PC12 cells. The thioflavine T (ThT) assay showed that 1 can effectively attenuate Cu²⁺-induced Aβ_1–42 aggregation. In addition, compound 1 is determined to be potent antioxidants on the basis of in vitro antioxidant assay, it can effectively decease the level of reactive oxygen species (ROS) in Cu²⁺-Aβ_1–42-treated PC12 cells and elevate the superoxide dismutase (SOD) activity in Cu²⁺-Aβ_1–42-treated PC12 cells. The results show that N,N′-1,10-bis(naringin) triethylenetetraamine is a potential agent for therapy of Alzheimer’s disease.

Graphical Abstract