Small Molecule Modulators of Copper-induced Abeta Aggregation

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Nov 3

PMID 19877631

Citations 62

Authors

Sarmad S Hindo

Allana M Mancino

Joseph J Braymer

Yihong Liu

Subramanian Vivekanandan

Ayyalusamy Ramamoorthy

Mi Hee Lim

Affiliations

Soon will be listed here.

Abstract

Our design of bifunctional metal chelators as chemical probes and potential therapeutics for Alzheimer's disease (AD) is based on the incorporation of a metal binding moiety into structural frameworks of Abeta aggregate-imaging agents. Using this strategy, two compounds 2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyridine-8-ol (1) and N(1),N(1)-dimethyl-N(4)-(pyridin-2-ylmethylene)benzene-1,4-diamine (2) were prepared and characterized. The bifunctionality for metal chelation and Abeta interaction of 1 and 2 was verified by spectroscopic methods. Furthermore, the reactivity of 1 and 2 with Cu(II)-associated Abeta aggregates was investigated. The modulation of Cu(II)-triggered Abeta aggregation by 1 and 2 was found to be more effective than that by the known metal chelating agents CQ, EDTA, and phen. These studies suggest a new class of multifunctional molecules for the development of chemical tools to unravel metal-associated events in AD and potential therapeutic agents for metal-ion chelation therapy.

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