title: Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors.
abstract: 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.
authors.affiliation: Institute of Chemistry, Faculty of Science, P. J. Safarik University , SK-041 67 Kosice, Slovak Republic.
authors.forename: Slavka
authors.initials: S
authors.lastname: Hamulakova
authors.forename: Ladislav
authors.initials: L
authors.lastname: Janovec
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinova
authors.forename: Katarina
authors.initials: K
authors.lastname: Spilovska
authors.forename: Jan
authors.initials: J
authors.lastname: Korabecny
authors.forename: Pavol
authors.initials: P
authors.lastname: Kristian
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jan
authors.initials: J
authors.lastname: Imrich
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D013619:Tacrine; C030123:coumarin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase