Tacrine based human cholinesterase inhibitors: Synthesis of peptidic-tethered derivatives and their effect on potency and selectivity

Tacrine based reversible inhibitors of cholinesterases (ChEIs) containing peptidic tethers were synthesized to interact with specific regions at the gorge level, and their potency was determined with human (h) acetylcholinesterase and butyrylcholinesterase. Analogues 3i,j and 3l,m were identified as promising hits and may pave the way for the development of a new series of tacrine based enzyme selective hChEIs.

Graphical abstractSynthesis and biological evaluation of tacrine based hChEIs containing specific peptidic tethers is described.Figure optionsDownload full-size imageDownload as PowerPoint slide