Original Publication Date: >1 June, 2017
Publication / Source: Future Medicinal Chemistry
Authors: Francisco Javier Pérez-Areales, Nibal Betari, Antonio Viayna et al
Aim: Simultaneous modulation of several key targets of the pathological network of Alzheimer’s disease (AD) is being increasingly pursued as a promising option to fill the critical gap of efficacious drugs against this condition. Materials & Methods: A short series of compounds purported to hit multiple targets of relevance in AD has been designed, on the basis of their distinct basicities estimated from high-level quantum mechanical computations, synthesized, and subjected to assays of inhibition of cholinesterases, BACE-1, and Aβ42 and tau aggregation, of antioxidant activity, and of brain permeation.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and a major cause of death worldwide . Because it is broadly accepted that AD is a multifactorial disorder, the development of drug candidates that simultaneously hit several key pathogenic factors is being increasingly pursued as a more realistic option to halt or slow the progression of the disease than compounds aimed at modulating a single molecular target [2–10]. Indeed, AD drug discovery is one of the fields in which the development of multitarget agents has experienced a greater growth in the past years . Multitarget compounds are usually designed by combining into hybrid molecules two or more pharmacophoric moieties that are known to enable the interaction with the selected molecular targets .
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