Preparation and in vitro screening of quartenary inhibitors of acetylcholinesterase

Abstract

Preparation and in vitro screening of quarternary inhibitors of acetylcholinesterase Abstract Reversible acetylcholinesterase (AChE) inhibitors are extensively used in human medicine. Among other applications they are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. For this purpose carbamate inhibitors are recently used (e.g. pyridostigmine chloride). Carbamates reversibly block AChE active site and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, these drugs have many undesirable side-effects and thus there are efforts to find a more suitable alternative among reversible AChE inhibitors. In this diploma thesis, 19 potential AChE inhibitors were prepared. Their ability to inhibit AChE and butyrylcholinesterase was evaluated in vitro and compared to selective standard cholinesterase inhibitors BW284c51 and ethopropazine. None of the prepared compounds was superior to used standards in inhibitory ability or selectivity. The structure activity relationship of the novel compounds was determinated from the obtained data