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.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | School of Science, Monash University Malaysia and Nanotechnology and Catalysis Research Centre, Universiti Malaya |
| Uncontrolled Keywords: | Alzheimer's disease; Blood-brain-barrier; Cholinesterase; Enzyme inhibition; Indazoles |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry T Technology > TP Chemical technology |
| Divisions: | Deputy Vice Chancellor (Research & Innovation) Office > Nanotechnology & Catalysis Research Centre |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 21 Jun 2024 03:27 |
| Last Modified: | 21 Jun 2024 03:27 |
| URI: | http://eprints.um.edu.my/id/eprint/44214 |
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