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Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase.

ABSTRACT: A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC₅₀) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC₅₀ value of 1.53 ± 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme.

SUBMITTER: Khunnawutmanotham N

PROVIDER: S-EPMC6204823 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase.

Khunnawutmanotham Nisachon N Laongthipparos Cherdchai C Saparpakorn Patchreenart P Chimnoi Nitirat N Techasakul Supanna S

Beilstein journal of organic chemistry 20181002

A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value o ...[more]

PMID: 30410615

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