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 IC(50) of 0.020 μM 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.
Huang
Ling
L
Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Luo
Zonghua
Z
He
Feng
F
Shi
Anding
A
Qin
Fangfei
F
Li
Xingshu
X
D000110:Acetylcholinesterase / Q000187:drug effects*; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000187:drug effects*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular
D002800:Cholinesterase Inhibitors; D001599:Berberine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase