Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile

Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile

Alzheimer's disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug target...

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Main Authors: Tobuse, Asuka Joy, Law, Christine Shing Wei, Thy, Chun Keng, James, Jason Jonah, Chee, Chin Fei, Yeong, Keng Yoon
Format: Article
Published: Springer Verlag 2024
Subjects:
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
TP Chemical technology
Online Access:http://eprints.um.edu.my/44214/
https://doi.org/10.1007/s00044-023-03179-8
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Institution: Universiti Malaya
id my.um.eprints.44214
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spelling my.um.eprints.442142024-06-21T03:27:06Z http://eprints.um.edu.my/44214/ Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile Tobuse, Asuka Joy Law, Christine Shing Wei Thy, Chun Keng James, Jason Jonah Chee, Chin Fei Yeong, Keng Yoon RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry TP Chemical technology Alzheimer's disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug targeting AD, particularly by inhibiting cholinesterase activity. Among the 17 indazole derivatives synthesized in this study, compound 4q was demonstrated to have potent and selective butyrylcholinesterase (BChE) inhibitory activity. Molecular docking simulations revealed that the binding of 4q with BChE was through hydrophobic and polar interactions. It was also found to easily permeate through the blood-brain-barrier via an in vitro model and is non-toxic when tested against SH-SY5Y cells. Springer Verlag 2024 Article PeerReviewed Tobuse, Asuka Joy and Law, Christine Shing Wei and Thy, Chun Keng and James, Jason Jonah and Chee, Chin Fei and Yeong, Keng Yoon (2024) Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile. Medicinal Chemistry Research, 33 (2). pp. 298-307. ISSN 1054-2523, DOI https://doi.org/10.1007/s00044-023-03179-8 <https://doi.org/10.1007/s00044-023-03179-8>. https://doi.org/10.1007/s00044-023-03179-8 10.1007/s00044-023-03179-8
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
TP Chemical technology
spellingShingle RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
TP Chemical technology
Tobuse, Asuka Joy
Law, Christine Shing Wei
Thy, Chun Keng
James, Jason Jonah
Chee, Chin Fei
Yeong, Keng Yoon
Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
description Alzheimer's disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug targeting AD, particularly by inhibiting cholinesterase activity. Among the 17 indazole derivatives synthesized in this study, compound 4q was demonstrated to have potent and selective butyrylcholinesterase (BChE) inhibitory activity. Molecular docking simulations revealed that the binding of 4q with BChE was through hydrophobic and polar interactions. It was also found to easily permeate through the blood-brain-barrier via an in vitro model and is non-toxic when tested against SH-SY5Y cells.
format Article
author Tobuse, Asuka Joy
Law, Christine Shing Wei
Thy, Chun Keng
James, Jason Jonah
Chee, Chin Fei
Yeong, Keng Yoon
author_facet Tobuse, Asuka Joy
Law, Christine Shing Wei
Thy, Chun Keng
James, Jason Jonah
Chee, Chin Fei
Yeong, Keng Yoon
author_sort Tobuse, Asuka Joy
title Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
title_short Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
title_full Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
title_fullStr Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
title_full_unstemmed Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
title_sort indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
publisher Springer Verlag
publishDate 2024
url http://eprints.um.edu.my/44214/
https://doi.org/10.1007/s00044-023-03179-8
_version_ 1805881136152313856

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