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.