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Synthesis and Biological Evaluation of Novel Tacrine Derivatives and Tacrine–Coumarin Hybrids as Cholinesterase Inhibitors

2014; American Chemical Society; Volume: 57; Issue: 16 Linguagem: Inglês

10.1021/jm5008648

1520-4804

Slávka Hamuľaková, Ladislav Janovec, Martina Hrabinová, Katarína Špilovská, Jan Korábečný, Pavol Kristián, Kamil Kuča, Ján Imrich,

Pesticide Exposure and Toxicity

A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were found to be the most potent inhibitors of human AChE (hAChE), demonstrating IC50 values of 0.0154 and 0.0263 μM. Ligands 6b, 6c, and 7c exhibited the highest levels of inhibitory activity against human BuChE (hBuChE), demonstrating IC50 values that range from 0.228 to 0.328 μM. Docking studies were performed in order to predict the binding modes of compounds 6b and 7c with hAChE/hBuChE.