title: Virtual screening discovery of new acetylcholinesterase inhibitors issued from CERMN chemical library.
abstract: In our quest to find new inhibitors able to inhibit acetylcholinesterase (AChE) and, at the same time, to protect neurons from beta amyloid toxicity, i.e., inhibitors interacting with the catalytic anionic subsite as well as with the peripherical anionic site of AChE, a virtual screening of the Centre d'Etudes et de Recherche sur le Medicament de Normandie (CERMN) chemical library was carried out. Two complementary approaches were applied, i.e., a ligand- and a structure-based screening. Each screening led to the selection of different compounds, but only two were present in both screening results. In vitro tests on AChE showed that one of those compounds presented a very good inhibition activity, of the same order as Donepezil. This result shows the real complementary of both methods for the discovery of new ligands.
authors.affiliation: Centre d'Etudes et de Recherche sur le Medicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Universite de Caen, UFR des Sciences Pharmaceutiques, boulevard Becquerel, Caen Cedex, France. jana.sopkova@unicaen.fr
authors.forename: Jana
authors.initials: J
authors.lastname: Sopkova-de Oliveira Santos
authors.forename: Aurelien
authors.initials: A
authors.lastname: Lesnard
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Agondanou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dupont
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Godard
authors.forename: Silvia
authors.initials: S
authors.lastname: Stiebing
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.forename: Frederic
authors.initials: F
authors.lastname: Fabis
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D000595:Amino Acid Sequence; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D014101:Torpedo / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D008024:Ligands; D054852:Small Molecule Libraries; D000110:Acetylcholinesterase