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Synthesis, kinetic evaluation and molecular docking studies of donepezil-based acetylcholinesterase inhibitors.

ABSTRACT: In an effort to develop new therapeutic agents to treat Alzheimer's disease, a series of donepezil-based analogs were designed, synthesized using an environmentally friendly route, and biologically evaluated for their inhibitory activity against electric eel acetylcholinesterase (AChE) enzyme. In vitro studies revealed that the phenyl moiety of donepezil can be successfully replaced with a pyridine ring leading to equally potent inhibitors of electric eel AChE. Further kinetic evaluations of the most potent inhibitor showed a dual-binding (mixed inhibition) mode, similar to donepezil. Molecular modeling studies suggest that several additional residues could be involved in the binding of this inhibitor in the human AChE enzyme active site compared to donepezil.

SUBMITTER: Makarian M

PROVIDER: S-EPMC8881002 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Synthesis, kinetic evaluation and molecular docking studies of donepezil-based acetylcholinesterase inhibitors.

Makarian Makar M Gonzalez Michael M Salvador Stephanie M SM Lorzadeh Shahrokh S Hudson Paula K PK Pecic Stevan S

Journal of molecular structure 20210903

In an effort to develop new therapeutic agents to treat Alzheimer's disease, a series of donepezil-based analogs were designed, synthesized using an environmentally friendly route, and biologically evaluated for their inhibitory activity against electric eel acetylcholinesterase (AChE) enzyme. <i>In vitro</i> studies revealed that the phenyl moiety of donepezil can be successfully replaced with a pyridine ring leading to equally potent inhibitors of electric eel AChE. Further kinetic evaluations ...[more]

PMID: 35221376

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