Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurological disorder, and multiple pathological factors are believed to be involved in the genesis and progression of the disease. A number of hypotheses, including Acetylcholinesterase, Monoamine oxidase, β-Amyloid, Tau protein, etc., have been proposed for the initiation and progression of the disease. At present, acetylcholine esterase inhibitors and memantine (NMDAR antagonist) are the only approved therapies for the symptomatic management of AD. Most of these single-target drugs have miserably failed in the treatment or halting the progression of the disease. Multi-factorial diseases like AD require complex treatment strategies that involve simultaneous modulation of a network of interacting targets. Since the last few years, Multi-Target-Directed Ligands (MTDLs) strategy, drugs that can simultaneously hit multiple targets, is being explored as an effective therapeutic approach for the treatment of AD. In the current review article, the authors have briefly described various pathogenic pathways associated with AD. The importance of Multi-Target-Directed Ligands and their design strategies in recently reported articles have been discussed in detail. Potent leads are identified through various structure-activity relationship studies, and their drug-like characteristics are described. Recently developed promising compounds have been summarized in the article. Some of these MTDLs with balanced activity profiles against different targets have the potential to be developed as drug candidates for the treatment of AD.