DESIGN AND SYNTHESIS OF SMALL MOLECULE INHIBITORS FOR AMYLOID and#946; Aand#946; AGGREGATION IN ALZHEIMER S DISEASE

Abstract

newline Alzheimer s disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration (FDA) has approved drugs (e.g. rivastigmine, donepezil, galantamine and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Considering the complex pathomechanism of AD, the most successful treatment strategies will likely take into account the new paradigm multi target directed ligands (MTDLs). As background information, here we reviewed the literature containing examples of MTDLs (especially small molecules) as inhibitors of butyrylcholinesterase (BuChE), acetylcholinesterase (AChE), and#947;and#8722;secretase, and#946;and#8722;secretase, tau misfolding, amyloidand#8722;and#946; (Aand#946;) aggregation and oxidative stress etc