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

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 1; pp. 51 - 56
• Main Authors: Guo, Li-Xia, Sun, Bin
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2021
• Subjects: Alzheimer’s disease; amyloid-beta; antioxidant; Cu2+ ion; naringin; Schiff base; Schiff base; amyloid-beta; naringin; antioxidant; Cu2+ ion; Alzheimer’s disease
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b20-00574

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 Aβ1–42 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+-Aβ1–42-treated PC12 cells and elevate the superoxide dismutase (SOD) activity in Cu2+-Aβ1–42-treated PC12 cells. The results show that N,N′-1,10-bis(naringin) triethylenetetraamine is a potential agent for therapy of Alzheimer’s disease.