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

Berberine derivatives with substituted amino groups linked on the 9-position of berberine with 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 value of 0.020μM for AchE. 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 0.020μM 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.