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Structure-based search for new inhibitors of cholinesterases.

ABSTRACT: Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer's disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC50 values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors.

SUBMITTER: Bajda M

PROVIDER: S-EPMC3634507 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Structure-based search for new inhibitors of cholinesterases.

Bajda Marek M Więckowska Anna A Hebda Michalina M Guzior Natalia N Sotriffer Christoph A CA Malawska Barbara B

International journal of molecular sciences 20130311 3

Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer's disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological eva ...[more]

PMID: 23478436

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