Virtual screening discovery of new acetylcholinesterase inhibitors issued from CERMN chemical library.
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.
Sopkova-de Oliveira Santos
Jana
J
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
Lesnard
Aurelien
A
Agondanou
Jean-Hugues
JH
Dupont
Nathalie
N
Godard
Anne-Marie
AM
Stiebing
Silvia
S
Rochais
Christophe
C
Fabis
Frederic
F
Dallemagne
Patrick
P
Bureau
Ronan
R
Rault
Sylvain
S
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
D002800:Cholinesterase Inhibitors; D008024:Ligands; D054852:Small Molecule Libraries; D000110:Acetylcholinesterase