Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents.

Abstract

Facing the multifactorial nature of Alzheimer's disease, twelve dibenzofuran/carbazole derivatives, which can be considered as the D-ring opened analogs of galantamine, have been designed and synthesized as multifunctional anti-Alzheimer agents. In vitro tests revealed that compounds 3 and 5, which bear a nitrate moiety in the molecule, showed a potent inhibition activity towards AChE and compound 3 showed a good Aβ42 aggregation inhibitory activity. Moreover, 3 and 5 could also release a relative low concentration of NO in vitro and they did not show toxicity to neuronal cells, while exerted a neuroprotective effect against the Aβ-induced toxicity. More importantly, compound 3 showed a significant spatial memory improving effect in vivo, and a good safety in the ex vivo toxicity study.

• Authors: Lei Fang, Xubin Fang, Shaohua Gou, Amelie Lupp, Isabell Lenhardt, Yanyan Sun, Zhangjian Huang, Yao Chen, Yihua Zhang, Christian Fleck
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 76 Pg. 376-86 (Apr 09 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 24594525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Cholinesterase Inhibitors
• Galantamine
• Nitric Oxide

Topics

• Alzheimer Disease (drug therapy)
• Animals
• Cholinesterase Inhibitors (chemical synthesis, chemistry, therapeutic use)
• Drug Design
• Female
• Galantamine (chemical synthesis, chemistry, therapeutic use)
• Magnetic Resonance Spectroscopy
• Microscopy, Atomic Force
• Nitric Oxide (metabolism)
• Rats
• Rats, Wistar
• Spectrometry, Mass, Electrospray Ionization