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A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease
[Display omitted] Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memant...
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| Published in: | Bioorganic chemistry 2024-03, Vol.144, p.107152-107152, Article 107152 |
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| Main Authors: | , |
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| container_end_page | 107152 |
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| container_start_page | 107152 |
| container_title | Bioorganic chemistry |
| container_volume | 144 |
| creator | Pathak, Chandni Kabra, Uma D. |
| description | [Display omitted]
Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy “one target, one molecule” has failed to provide promising therapeutic effects due to the multifactorial nature of AD. This triggered the development of a novel strategy called Multi-Target Directed Ligand (MTDL) which involved designing one molecule that acts on multiple targets simultaneously. The present review discusses the detailed pathology involved in AD and the various MTDL design strategies bearing different heterocycles, in vitro and in vivo activities of the compounds, and their corresponding structure–activity relationships. This knowledge will allow us to identify and design more effective MTDLs for the treatment of AD. |
| doi_str_mv | 10.1016/j.bioorg.2024.107152 |
| format | article |
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Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy “one target, one molecule” has failed to provide promising therapeutic effects due to the multifactorial nature of AD. This triggered the development of a novel strategy called Multi-Target Directed Ligand (MTDL) which involved designing one molecule that acts on multiple targets simultaneously. The present review discusses the detailed pathology involved in AD and the various MTDL design strategies bearing different heterocycles, in vitro and in vivo activities of the compounds, and their corresponding structure–activity relationships. This knowledge will allow us to identify and design more effective MTDLs for the treatment of AD.</description><identifier>ISSN: 0045-2068</identifier><identifier>EISSN: 1090-2120</identifier><identifier>DOI: 10.1016/j.bioorg.2024.107152</identifier><identifier>PMID: 38290187</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acetylcholinesterase ; Alzheimer Disease - drug therapy ; Alzheimer Disease - pathology ; Alzheimer’s disease ; Amyloid β aggregation ; Butyrylcholinesterase ; Cholinesterase inhibitors ; Cholinesterase Inhibitors - pharmacology ; Cholinesterase Inhibitors - therapeutic use ; Dementia ; Donepezil - therapeutic use ; Humans ; Ligands ; Multi-target directed ligand ; Oxidative stress ; Rivastigmine - therapeutic use</subject><ispartof>Bioorganic chemistry, 2024-03, Vol.144, p.107152-107152, Article 107152</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-77b71a60b493dd110d484c958f1d8202764fcafac47f225ef692fbbb42a6f9283</citedby><cites>FETCH-LOGICAL-c362t-77b71a60b493dd110d484c958f1d8202764fcafac47f225ef692fbbb42a6f9283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38290187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pathak, Chandni</creatorcontrib><creatorcontrib>Kabra, Uma D.</creatorcontrib><title>A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease</title><title>Bioorganic chemistry</title><addtitle>Bioorg Chem</addtitle><description>[Display omitted]
Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy “one target, one molecule” has failed to provide promising therapeutic effects due to the multifactorial nature of AD. This triggered the development of a novel strategy called Multi-Target Directed Ligand (MTDL) which involved designing one molecule that acts on multiple targets simultaneously. The present review discusses the detailed pathology involved in AD and the various MTDL design strategies bearing different heterocycles, in vitro and in vivo activities of the compounds, and their corresponding structure–activity relationships. This knowledge will allow us to identify and design more effective MTDLs for the treatment of AD.</description><subject>Acetylcholinesterase</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer’s disease</subject><subject>Amyloid β aggregation</subject><subject>Butyrylcholinesterase</subject><subject>Cholinesterase inhibitors</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>Dementia</subject><subject>Donepezil - therapeutic use</subject><subject>Humans</subject><subject>Ligands</subject><subject>Multi-target directed ligand</subject><subject>Oxidative stress</subject><subject>Rivastigmine - therapeutic use</subject><issn>0045-2068</issn><issn>1090-2120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kMtKAzEUhoMotl7eQCRLN1OTNDOZ2QileIOCG12HTHLSpsylJqmiK1_D1_NJTBl16erA4f_Oz_kQOqNkQgktLteT2vW9X04YYTytBM3ZHhpTUpGMUUb20ZgQnmeMFOUIHYWwJoRSLopDNJqWrCK0FGOkZlj37cbDCrrgXgB7eHHwinuL220TXRaVX0LExnnQEQxu3FJ1JmDX4bgCHD2o2EIXd8SseV-Ba8F_fXyGhARQAU7QgVVNgNOfeYyebq4f53fZ4uH2fj5bZHpasJgJUQuqClLzamoMpcTwkusqLy01ZXpRFNxqZZXmwjKWgy0qZuu65kwVtmLl9BhdDHc3vn_eQoiydUFD06gO-m2QrGIkF8lAlaJ8iGrfh-DByo13rfJvkhK5kyvXcpArd3LlIDdh5z8N27oF8wf92kyBqyEA6c-k0cugHXQaBnvS9O7_hm8T9Y5M</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Pathak, Chandni</creator><creator>Kabra, Uma D.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202403</creationdate><title>A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease</title><author>Pathak, Chandni ; Kabra, Uma D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-77b71a60b493dd110d484c958f1d8202764fcafac47f225ef692fbbb42a6f9283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acetylcholinesterase</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer’s disease</topic><topic>Amyloid β aggregation</topic><topic>Butyrylcholinesterase</topic><topic>Cholinesterase inhibitors</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>Dementia</topic><topic>Donepezil - therapeutic use</topic><topic>Humans</topic><topic>Ligands</topic><topic>Multi-target directed ligand</topic><topic>Oxidative stress</topic><topic>Rivastigmine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pathak, Chandni</creatorcontrib><creatorcontrib>Kabra, Uma D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pathak, Chandni</au><au>Kabra, Uma D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease</atitle><jtitle>Bioorganic chemistry</jtitle><addtitle>Bioorg Chem</addtitle><date>2024-03</date><risdate>2024</risdate><volume>144</volume><spage>107152</spage><epage>107152</epage><pages>107152-107152</pages><artnum>107152</artnum><issn>0045-2068</issn><eissn>1090-2120</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Review-1</notes><abstract>[Display omitted]
Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy “one target, one molecule” has failed to provide promising therapeutic effects due to the multifactorial nature of AD. This triggered the development of a novel strategy called Multi-Target Directed Ligand (MTDL) which involved designing one molecule that acts on multiple targets simultaneously. The present review discusses the detailed pathology involved in AD and the various MTDL design strategies bearing different heterocycles, in vitro and in vivo activities of the compounds, and their corresponding structure–activity relationships. This knowledge will allow us to identify and design more effective MTDLs for the treatment of AD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38290187</pmid><doi>10.1016/j.bioorg.2024.107152</doi><tpages>1</tpages></addata></record> |
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| ispartof | Bioorganic chemistry, 2024-03, Vol.144, p.107152-107152, Article 107152 |
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| language | eng |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Acetylcholinesterase Alzheimer Disease - drug therapy Alzheimer Disease - pathology Alzheimer’s disease Amyloid β aggregation Butyrylcholinesterase Cholinesterase inhibitors Cholinesterase Inhibitors - pharmacology Cholinesterase Inhibitors - therapeutic use Dementia Donepezil - therapeutic use Humans Ligands Multi-target directed ligand Oxidative stress Rivastigmine - therapeutic use |
| title | A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease |
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