Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates.
Five tacrine-ferulic acid hybrids (6a-e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates. All target compounds have better acetylcholinesterase inhibitory activity and comparable butyrylcholinesterase inhibitory activity in relation to tacrine. Interestingly, 6d showed a reversible and non-competitive inhibitory action for acetylcholinesterase indicating interaction with the peripheral anionic site, whereas a reversible but competitive inhibitory action for butyrylcholinesterase. The antioxidant study revealed that four target compounds have, compared to Trolox, high ability to absorb reactive oxygen species.
Fang
Lei
L
Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.
Kraus
Birgit
B
Lehmann
Jochen
J
Heilmann
Joerg
J
Zhang
Yihua
Y
Decker
Michael
M
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D002839:Chromans; D003373:Coumaric Acids; D017382:Reactive Oxygen Species; D013619:Tacrine; C004999:ferulic acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid