Design, synthesis and evaluation of multifunctional salphen derivatives for the treatment of Alzheimer's disease.

Abstract

A series of salphen derivatives (1-26) have been designed, synthesized, and evaluated as chemical reagents that target and modulate multiple facets of Alzheimer's disease. Most of the compounds exhibit a significant ability to inhibit self-induced and Cu(2+)-induced β-amyloid (Aβ1-42) aggregation, and to function as potential antioxidants and biometal chelators. In particular, the antioxidant activity of compound 2 is 2.6-fold of the trolox value by using the ABTS radical scavenging method, and it also shows a significant ability to inhibit self-induced and Cu(2+)-induced β-amyloid (Aβ1-42) aggregation (70.3%, 20 μM and 85.7%, 50 μM, respectively). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu(2+)-Aβ, shows a good neuroprotective effect in human SH-SY5Y neuroblastoma cells and can cross the blood-brain barrier. In addition, compound 2 retains the activities of antioxidant, anti Aβ aggregation and neuroprotection after capturing the metal ions Cu(2+), Fe(3+) and Zn(2+) (its metal complexes 18, 22 and 23). Taken together, these results suggest that compound 2 might be a promising lead compound for AD treatment.

• Authors: Neng Jiang, Su-Yi Li, Sai-Sai Xie, Zhong-Rui Li, Kelvin D G Wang, Xiao-Bing Wang, Ling-Yi Kong
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 87 Pg. 540-51 (Nov 24 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 25290683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Neuroprotective Agents
• Phenylenediamines
• salphen

Topics

• Alzheimer Disease (drug therapy)
• Blood-Brain Barrier
• Cell Line, Tumor
• Drug Design
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Docking Simulation
• Neuroprotective Agents (chemical synthesis, chemistry, therapeutic use)
• Phenylenediamines (chemical synthesis, chemistry, therapeutic use)
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Infrared