Journal
CURRENT MEDICINAL CHEMISTRY
Volume 29, Issue 10, Pages 1757-1803Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867328666210512005508
Keywords
Alzheimer's disease; acetylcholinesterase; monoamine oxidase; beta-amyloid; multi-target directed ligands; MTDLs
Funding
- Council of Scientific and Industrial Research New Delhi [02/(0354)/19/EMRII]
- Department of Science and Technology
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Alzheimer's disease is a complex neurological disorder with multiple pathological factors involved. The use of single-target drugs has been unsuccessful in treating the disease, highlighting the importance of multi-target-directed ligands as a potential therapeutic approach.
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, beta-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.
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