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

Ling Huang; Zonghua Luo; Feng He; Anding Shi; Fangfei Qin; Xingshu Li

doi:10.1016/j.bmcl.2010.09.013

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

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6649-52. doi: 10.1016/j.bmcl.2010.09.013. Epub 2010 Sep 15.

Authors

Ling Huang¹, Zonghua Luo, Feng He, Anding Shi, Fangfei Qin, Xingshu Li

Affiliation

¹ Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

PMID: 20880702
DOI: 10.1016/j.bmcl.2010.09.013

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / drug effects*
Berberine / chemistry
Berberine / pharmacology*
Butyrylcholinesterase / drug effects*
Catalytic Domain
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Models, Molecular

Substances

Cholinesterase Inhibitors
Berberine
Acetylcholinesterase
Butyrylcholinesterase