Title:Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease
Volume: 29
Issue: 10
Author(s): Bhupinder Kumar, Amandeep Thakur, Ashish Ranjan Dwivedi, Rakesh Kumar*Vinod Kumar*
Affiliation:
- Department of Chemistry, School of Basic and Applied
Sciences, Central University of Punjab, Bathinda, Punjab, 151001, India
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda,
Punjab, 151001, India
- Laboratory of Organic and Medicinal
Chemistry, Department of Chemistry, Central University of Punjab, Bathinda, Punjab, 151001, India
Keywords:
Alzheimer’s disease, acetylcholinesterase, monoamine oxidase, β-amyloid, multi-target directed ligands, MTDLs.
Abstract: 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 hypothesis 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 therapy 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 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 the AD. Importance of Multi-Target-Directed Ligands and their
design strategies in recently reported articles have been discussed in detail. Potent leads
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 profile against different
targets have the potential to be developed as drug candidates for the treatment of AD.
