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Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel a...

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Autores principales: Sharma, Pratibha, Singh, Manjinder, Singh, Varinder, Singh, Thakur Gurjeet, Singh, Tanveer, Ahmad, Sheikh F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534526/
https://www.ncbi.nlm.nih.gov/pubmed/37764355
http://dx.doi.org/10.3390/molecules28186579
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author Sharma, Pratibha
Singh, Manjinder
Singh, Varinder
Singh, Thakur Gurjeet
Singh, Tanveer
Ahmad, Sheikh F.
author_facet Sharma, Pratibha
Singh, Manjinder
Singh, Varinder
Singh, Thakur Gurjeet
Singh, Tanveer
Ahmad, Sheikh F.
author_sort Sharma, Pratibha
collection PubMed
description No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC(50) = 15.3 nM), even more than the standard drug (IC(50) = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.
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spelling pubmed-105345262023-09-29 Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease Sharma, Pratibha Singh, Manjinder Singh, Varinder Singh, Thakur Gurjeet Singh, Tanveer Ahmad, Sheikh F. Molecules Article No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC(50) = 15.3 nM), even more than the standard drug (IC(50) = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules. MDPI 2023-09-12 /pmc/articles/PMC10534526/ /pubmed/37764355 http://dx.doi.org/10.3390/molecules28186579 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sharma, Pratibha
Singh, Manjinder
Singh, Varinder
Singh, Thakur Gurjeet
Singh, Tanveer
Ahmad, Sheikh F.
Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title_full Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title_fullStr Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title_full_unstemmed Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title_short Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
title_sort recent development of novel aminoethyl-substituted chalcones as potential drug candidates for the treatment of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534526/
https://www.ncbi.nlm.nih.gov/pubmed/37764355
http://dx.doi.org/10.3390/molecules28186579
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