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Tacrine– F lurbiprofen Hybrids as Multifunctional Drug Candidates for the Treatment of Alzheimer's Disease
Author(s) -
Chen Yao,
Sun Jianfei,
Peng Sixun,
Liao Hong,
Zhang Yihua,
Lehmann Jochen
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300074
Subject(s) - tacrine , flurbiprofen , acetylcholinesterase , chemistry , butyrylcholinesterase , inhibitory postsynaptic potential , aché , pharmacology , cholinesterase , in vitro , drug , biochemistry , enzyme , medicine
Five tacrine–flurbiprofen hybrid compounds ( 3a – e ) were synthesized as multi‐target‐directed compounds for the treatment of Alzheimer's disease. Compared to tacrine, two compounds ( 3d and 3e ) showed better acetylcholinesterase (AChE) inhibitory activity and others ( 3b – e ) better or the same butyrylcholinesterase (BuChE) inhibitory activity. Notably, 3d showed a mixed‐type inhibitory action for AChE, indicating a “dual‐binding site action” of both toward the catalytic active site (CAS) and the peripheral anionic site (PAS), whereas for BuChE, a competitive inhibitory action was observed. Furthermore, a cell‐based assay on amyloid‐β inhibition demonstrated that the selected target compound 3d effectively inhibits the formation of amyloid‐β in vitro .