New Potent Acetylcholinesterase Inhibitors in the Tetracyclic Triterpene Series

A new highly selective inhibitor of acetylcholinesterase (AChE) was discovered by high-throughput screening.
Compound 1 was synthesized from a natural product, the N-3-isobutyrylcycloxobuxidine-F 2. A new extraction
protocol of this compound is described. The hemisynthesis and optimization of 1 are reported. The analogs
of 1 were tested in vitro for the inhibition of both cholinesterases (AChE and BuChE). These compounds
selectively inhibited AChE. Extensive molecular docking studies were performed with 2 and AChE employing
Discover Biosym software to rationalize the binding interaction. The results suggested that ligand 2 binds
simultaneously to both catalytic and peripheral sites of AChE.