Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May 1;20(9):2987-90.
doi: 10.1016/j.bmcl.2010.02.102. Epub 2010 Mar 3.

Peripheral site acetylcholinesterase inhibitors targeting both inflammation and cholinergic dysfunction

Sherri Young  1 , Karine Fabio, Christophe Guillon, Pramod Mohanta, Timothy A Halton, Diane E Heck, Robert A Flowers 2nd, Jeffrey D Laskin, Ned D Heindel
Affiliations

Peripheral site acetylcholinesterase inhibitors targeting both inflammation and cholinergic dysfunction

Sherri Young et al. Bioorg Med Chem Lett. .

Abstract

The design and study of two classes of noncompetitive acetylcholinesterase inhibitors (AChEIs) which also function as NSAID prodrugs are reported. The most potent AChEIs disclosed contain an aromatic alkyl-aryl linker between an NSAID and a lipophilic choline mimic and they inhibit acetylcholinesterase (AChE) in the submicromolar range. These agents have the therapeutic potential to dually target inflammation by releasing an NSAID in vivo and activating the cholinergic anti-inflammatory pathway via cholinergic up-regulation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Generic Structures of Class 1 (top) and Class 2 (bottom) agents.
Figure 2
Figure 2
Structure of 7, the most potent AChEI discussed herein (IC50 = 0.51 μM).
Scheme 1
Scheme 1
Synthesis of Class 1 agents. a) Et3N, THF, −10 to 25°C; b) NSAID, EDC HCl, DMAP, CH2Cl2, 0 to 25°C.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Özgüney I. Expert Opin Pharmacother. 2008;9:1805–1816. - PubMed
    1. Deeva I, Mariani S, De Luca C, Pacifico V, Leoni L, Raskovic D, Kharaeva Z, Korkina L, Pastore S. Wide-spectrum profile of inflammatory mediators in the plasma and scales of patients with psoriatic disease. Cytokine. 2009 doi: 10.1016/j.cyto.2009.09.014. - DOI - PubMed
    1. Centonze D, Muzio L, Rossi S, Furlan R, Bernardi G, Martino G. The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death & Diff. 2009 doi: 10.1038/cdd.2009.179. - DOI - PubMed
    1. Kunz M, Ibrahim S. Mediators Inflamm. 2009;2009:1–20. - PMC - PubMed
    1. Cannon J. Pharmacology for Chemists. 2. Oxford University Press; New York: Concepts of Pharmacology; pp. 13–17.

Publication types

MeSH terms

LinkOut - more resources