4.3 Article

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

Journal

BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 44, Issue 1, Pages 51-56

Publisher

PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b20-00574

Keywords

naringin; Schiff base; Cu2+ ion; amyloid-beta; antioxidant; Alzheimer's disease

Funding

  1. Natural Science Foundation of China [81603173]
  2. Chongqing Municipal Education Committee [KJ1600607]
  3. Chongqing Science & Technology committee [cstc2018jcyjAX0754, cstc2020jcyj-msxmX0830]
  4. Key Projects of Basic Science and Advanced Technology Research of Chongqing City [cstc2015jcyjBX0125]
  5. Chongqing technology and Business University [1352002]
  6. Key Laboratory of Natural Medicine Research of Chongqing Education Commission [CQCM-2017-09, CQCM-2016-09]

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The bis-Schiff base of N,N'-1,10-bis(naringin) triethylenetetraamine shows potential as a therapy for Alzheimer's disease by promoting PC12 cell proliferation, inhibiting Cu2+-amyloid-beta mediated cytotoxicity, and attenuating A beta(1-42) aggregation. Additionally, the compound acts as a potent antioxidant by decreasing ROS levels and increasing SOD activity in treated cells.
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-beta (A beta)(1-42) mediated cytotoxicity on PC12 cells. The thioflavine T (ThT) assay showed that 1 can effectively attenuate Cu2+-induced A beta(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+-A beta(1-42) -treated PC12 cells and elevate the superoxide dismutase (SOD) activity in Cu2+-A beta(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.

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