Conceptual Framework of the Design of Pleiotropic Drugs against Alzheimer’s Disease

Abstract

The multifactorial nature of some diseases, particularly neurodegenerative diseases such as Alzheimer’s disease, frequently requires the use of several drugs. These drug cocktails are not without drawbacks in terms of increased adverse effects, drug–drug interactions or low adherence to treatment. The use of pleiotropic drugs, which combine, within a single molecule, several activities directed against distinct therapeutic targets, makes it possible to overcome some of these problems. In addition, these pleiotropic drugs generally lead to the expression of a synergy of effects, sometimes greater than that observed with a combination of drugs. This article will review, through recent examples, the different kinds of pleiotropic drugs being studied or already present on the market of medicines, with a focus on the structural aspect of such drug design.

New Multitarget Rivastigmine–Indole Hybrids as Potential Drug Candidates for Alzheimer’s Disease

“…In view of this, there is a current strategy for drug development, based on multitarget directed ligands (MTDL), to enable the simultaneous hitting of several of the most important targets associated with AD instead of pursuing the current single-target drugs. Hence, medicinal chemists have been working to design single drugs with multiple pharmacophores that can act on the various targets of AD, including cholinergic and amyloidogenic processes, oxidative stress, neuroinflammation, metal chelation and also inhibition of other enzymes with significant roles in these neurodegenerative processes [ 15 , 16 , 17 , 18 , 19 ].…”

A Multitarget Approach against Neuroinflammation: Alkyl Substituted Coumarins as Inhibitors of Enzymes Involved in Neurodegeneration

“…These extremely disabling pathologies, for which there are still no effective cures, are characterized by a multifactorial etiology [1,3]. In this context, the therapy of neurodegenerative disorders could take advantage of multi-target directed ligands (MTDLs) which are able to affect impaired cellular mechanisms of these conditions [4][5][6][7]. In the light of the role that human monoamine oxidase B (MAO-B) as well as acetylcholinesterase and butyrylcholinesterase (AChE and BuChE) play in neurodegenerative disorders, MTDLs are often directed to these targets [8][9][10].…”