title: Synthesis, characterization and in vitro evaluation of substituted N-(2-phenylcyclopropyl)carbamates as acetyl- and butyrylcholinesterase inhibitors.
abstract: A serie of O-substituted N-2-phenylcyclopropylcarbamates was prepared and characterized. These carbamates were tested as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was found, that these compounds exhibit moderate inhibition activity with values of IC50in the range of 54.8-94.4 μM (for AChE) and up to 5.8 μM (for BChE). The AChE/BChE selectivity for each carbamate was calculated. These values varied from 0.50 to 9.46, two carbamate derivatives inhibited only AChE selectively. The most promising derivative was prepared in all optically pure forms (four isomers). It was found that individual stereoisomers differed only slightly in the inhibition ability. The cytotoxicity of all carbamates was evaluated using the standard in vitro test with Jurkat cells. With regard to their inhibition activity and cytotoxicity as well as easy preparation, O-substituted N-2-phenylcyclopropylcarbamates can be considered as promising compounds for potential medicinal applications.
authors.affiliation: a Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic and.
authors.forename: Eva
authors.initials: E
authors.lastname: Horáková
authors.affiliation: a Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic and.
authors.forename: Pavel
authors.initials: P
authors.lastname: Drabina
authors.affiliation: a Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic and.
authors.forename: Břetislav
authors.initials: B
authors.lastname: Brož
authors.affiliation: b Department of Biological and Biochemical Sciences , Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Štěpánková
authors.affiliation: b Department of Biological and Biochemical Sciences , Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic.
authors.forename: Katarína
authors.initials: K
authors.lastname: Vorčáková
authors.affiliation: b Department of Biological and Biochemical Sciences , Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Královec
authors.affiliation: b Department of Biological and Biochemical Sciences , Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Havelek
authors.affiliation: a Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice , Pardubice , Czech Republic and.
authors.forename: Miloš
authors.initials: M
authors.lastname: Sedlák
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; C000614353:N-(2-phenylcyclopropyl)carbamate; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Carbamates; cholinesterase inhibitors; cyclopropane derivatives; in vitro cytotoxicity; lipophilicity