Maqsood Cheema, Z., Nisar, M., Yasmeen Gondal, H. et al. (3 more authors) (2023) New benzotriazole-derived α-substituted hemiaminal ethers with enhanced cholinesterase inhibition activity: synthesis, structural, and biological evaluations. Journal of Saudi Chemical Society, 27 (6). 101746. ISSN 1319-6103
Abstract
A new series of benzotriazole-derived α-substituted hemiaminal ethers have been synthesized as human cholinesterase (hChE) inhibitors with enhanced activity. The synthesized compounds were extensively characterized by 1H NMR and 13C NMR spectroscopy, mass spectrometry, and SC-XRD studies. All the compounds demonstrated dual inhibition potential against acetyl and butylcholinesterases (AChE and BChE) in the in-vitro studies. Results revealed that compounds carrying the optically active (R)-menthol group demonstrated more activity than the bicyclic (R)-fenchol moiety. For instance, α-butyl-(R)-menthyl-benzotriazole derivative (5a-iii) exhibited the best AChE inhibition with an IC50 value of 44.03 nM, while its α-methyl analog (5a-i) showed promising results against BChE inhibition (IC50 = 80.74 nM). The molecular modeling study was carried out to assess the binding interactions with the target proteins to rationalize the structural–activity relationship. Subsequently, the stability of the protein–ligand complex was verified through molecular dynamics (MD) simulations. Pharmacokinetic and bioavailability parameters further supported the suitability of the new inhibitors as lead compounds for neurological disorders.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | Hemiaminal ethers; Benzotriazole; Cholinesterases; Alzheimer’s Disease; (R)-menthol; (R)-fenchyl alcohol; Neurological disorders |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2024 16:06 |
Last Modified: | 31 Jan 2024 16:06 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.jscs.2023.101746 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:208172 |