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Discovery of new acetylcholinesterase inhibitors for Alzheimer's disease: virtual screening and in vitro characterisation.

ABSTRACT: For more than two decades, the development of potent acetylcholinesterase (AChE) inhibitors has been an ongoing task to treat dementia associated with Alzheimer's disease and improve the pharmacokinetic properties of existing drugs. In the present study, we used three docking-based virtual screening approaches to screen both ZINC15 and MolPort databases for synthetic analogs of physostigmine and donepezil, two highly potent AChE inhibitors. We characterised the in vitro inhibitory concentration of 11 compounds, ranging from 14 to 985 μM. The most potent of these compounds, S-I 26, showed a fivefold improved inhibitory concentration in comparison to rivastigmine. Moderate inhibitors carrying novel scaffolds were identified and could be improved for the development of new classes of AChE inhibitors.

SUBMITTER: David B

PROVIDER: S-EPMC7833026 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Discovery of new acetylcholinesterase inhibitors for Alzheimer's disease: virtual screening and <i>in vitro</i> characterisation.

David Benoit B Schneider Pascal P Schäfer Philipp P Pietruszka Jörg J Gohlke Holger H

Journal of enzyme inhibition and medicinal chemistry 20211201 1

For more than two decades, the development of potent acetylcholinesterase (AChE) inhibitors has been an ongoing task to treat dementia associated with Alzheimer's disease and improve the pharmacokinetic properties of existing drugs. In the present study, we used three docking-based virtual screening approaches to screen both ZINC15 and MolPort databases for synthetic analogs of physostigmine and donepezil, two highly potent AChE inhibitors. We characterised the <i>in vitro</i> inhibitory concent ...[more]

PMID: 33478277

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