Preparation, in vitro screening and molecular modelling of monoquaternary compounds related to the selective acetylcholinesterase inhibitor BW284c51.
This paper describes preparation and in vitro evaluation of 19 compounds related to the selective experimental cholinesterase inhibitor BW284c51. The novel compounds were prepared as fragments of parent molecule BW284c51 and evaluated on the model of human recombinant acetylcholinesterase and human plasmatic butyrylcholinesterase. The IC₅₀ values of the prepared compounds were compared to the parent molecule BW284c51. None of the compounds was superior to the parent drug, but two BW284c51 fragments showed promising hAChE inhibition in µM scale and improved selectivity. These two fragments were further subjected to the molecular modelling study and their enzyme interactions were rationalized. The structure-activity relationship of the prepared series was stated.
Ondrej
O
Benek
Kamil
K
Musilek
Anna
A
Horova
Vlastimil
V
Dohnal
Rafael
R
Dolezal
University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. kamil.kuca@fnhk.cz.
Kamil
K
Kuca
D000110:Acetylcholinesterase / Q000737:chemistry*; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / Q000737:chemistry*; D002091:Butyrylcholinesterase / Q000737:chemistry*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase