Novel aromatic–polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase

Three types of aromatic–polyamine conjugates (6a–6s) were designed, synthesized and evaluated as potential inhibitors for cholinesterases (ChEs). The results showed that anthraquinone–polyamine conjugates (AQPCs) exhibited the most potent acetylcholinesterase (AChE) inhibitory activity with IC50 values from 1.50 to 11.13 μM. Anthracene–polyamine conjugates (APCs) showed a surprising selectivity (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase (BChE), with IC50 values from 0.016 to 0.657 μM. A Lineweaver–Burk plot and molecular modeling studies indicated that the representative compounds, 6l and 6k, targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of ChEs. Furthermore, APCs did not affect HepG2 cell viability at the concentration of 100 μM. Consequently, these polyamine conjugates could be thoroughly and systematically studied for the treatment of AD.

Three types of novel aromatic–polyamine conjugates were synthesized as cholinesterase inhibitors. Anthracene–polyamine conjugates (6h–6o) showed a surprising selectivity (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase, with some IC50 values from 0.016 to 0.657 μM. And they did not affect HepG2 cell viability at the concentration of 100 μM.Figure optionsDownload as PowerPoint slide