Preparation, In Vitro Screening and Molecular Modelling of Monoquaternary Compounds Related to the Selective Acetylcholinesterase Inhibitor BW284c51
Ondrej Benek, Kamil Musilek, Anna Horova, Vlastimil Dohnal, Rafael Dolezal and Kamil Kuca
Affiliation: University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
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.
Keywords: Acetylcholinesterase inhibitor, BW284c51, synthesis, in vitro, molecular modelling.
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