Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multi-functional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation.
A series of 9-N-substituted berberine derivatives were synthesized and biologically evaluated as antioxidant and inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase and amyloid-β aggregation. Most of these compounds exhibited very good antioxidant activities, inhibitive activities of AChE and amyloid-β aggregation. Among them, compound 8d, (o-methylphenethyl)amino linked at the 9-position of berberine, was found to be a good antioxidant (with 4.05 μM of Trolox equivalents), potent inhibitor of AChE (an IC(50) value of 0.027 μM), and high active inhibitor of amyloid-β aggregation (an IC(50) value of 2.73 μM).
Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Wen-Jun
WJ
Shan
Ling
L
Huang
Qi
Q
Zhou
Fan-Chao
FC
Meng
Xing-Shu
XS
Li
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D006736:Horses; D006801:Humans; D008958:Models, Molecular
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D001599:Berberine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase