title: Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors.
abstract: A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, (1)H, (13)C and (19)F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.
authors: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-532 10 Pardubice, Czech Republic. Ales.Imramovsky@upce.cz
authors: Aleš
authors: A
authors: Imramovský
authors: Vladimír
authors: V
authors: Pejchal
authors: Šárka
authors: Š
authors: Štěpánková
authors: Katarína
authors: K
authors: Vorčáková
authors: Josef
authors: J
authors: Jampílek
authors: Ján
authors: J
authors: Vančo
authors: Petr
authors: P
authors: Šimůnek
authors: Karel
authors: K
authors: Královec
authors: Lenka
authors: L
authors: Brůčková
authors: Jana
authors: J
authors: Mandíková
authors: František
authors: F
authors: Trejtnar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D054879:Halogenation; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D013844:Thiazoles; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase