Berberine derivatives, with substituted amino groups linked at the 9-position, as inhibitors of acetylcholinesterase/butyrylcholinesterase

Berberine derivatives with substituted amino groups linked at the 9-position using different carbon spacers were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Compound 10b, with a cyclohexylamino group linked to berberine by a three carbon spacer, gave the most potent inhibitor activity with an IC50 of 0.020 mu M for AChE. Kinetic studies revealed mixed inhibition of AChE, and molecular modeling simulations of the AChE-inhibitor complex confirmed that compounds bound to both the catalytic active site and the peripheral anionic site. (C) 2010 Elsevier Ltd. All rights reserved.