Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment

Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead mol...

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Autores principales: Gupta, Shraddha Manish, Behera, Ashok, Jain, Neetesh K., Tripathi, Avanish, Rishipathak, Dinesh, Singh, Siddharth, Ahemad, Nafees, Erol, Meryem, Kumar, Devendra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476022/
https://www.ncbi.nlm.nih.gov/pubmed/37671344
http://dx.doi.org/10.1039/d3ra03224h
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author Gupta, Shraddha Manish
Behera, Ashok
Jain, Neetesh K.
Tripathi, Avanish
Rishipathak, Dinesh
Singh, Siddharth
Ahemad, Nafees
Erol, Meryem
Kumar, Devendra
author_facet Gupta, Shraddha Manish
Behera, Ashok
Jain, Neetesh K.
Tripathi, Avanish
Rishipathak, Dinesh
Singh, Siddharth
Ahemad, Nafees
Erol, Meryem
Kumar, Devendra
author_sort Gupta, Shraddha Manish
collection PubMed
description Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC(50): 4.16 ± 0.063 μM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aβ aggregation at 0.5, 10 and 20 μM doses. Approximately, 50% of AChE-induced Aβ aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.
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spelling pubmed-104760222023-09-05 Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment Gupta, Shraddha Manish Behera, Ashok Jain, Neetesh K. Tripathi, Avanish Rishipathak, Dinesh Singh, Siddharth Ahemad, Nafees Erol, Meryem Kumar, Devendra RSC Adv Chemistry Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC(50): 4.16 ± 0.063 μM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aβ aggregation at 0.5, 10 and 20 μM doses. Approximately, 50% of AChE-induced Aβ aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD. The Royal Society of Chemistry 2023-09-04 /pmc/articles/PMC10476022/ /pubmed/37671344 http://dx.doi.org/10.1039/d3ra03224h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Gupta, Shraddha Manish
Behera, Ashok
Jain, Neetesh K.
Tripathi, Avanish
Rishipathak, Dinesh
Singh, Siddharth
Ahemad, Nafees
Erol, Meryem
Kumar, Devendra
Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title_full Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title_fullStr Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title_full_unstemmed Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title_short Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
title_sort development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for alzheimer's treatment
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476022/
https://www.ncbi.nlm.nih.gov/pubmed/37671344
http://dx.doi.org/10.1039/d3ra03224h
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