title: Isoxazolotacrines as non-toxic and selective butyrylcholinesterase inhibitors for Alzheimer's disease.
abstract: BACKGROUND
  Owing to the complex nature of Alzheimer's disease, there is a renewed and growing search for multitarget non-toxic tacrines as simple, easily available drugs in order to stop the progress and development of the disease.
  
  
  RESULTS
  This paper describes our preliminary results on the synthesis, in vitro biochemical evaluation and molecular modeling of isoxazolotacrines as potential drugs for the treatment of Alzheimer's disease. Novel 3-phenyl-5,6,7,8-tetrahydroisoxazolo[5,4-b]quinolin-4-amine (OC41) is a promising, 31% less toxic than tacrine in HepG2 cells, and selective reversible human butyrylcholinesterase inhibitor (IC50 = 5.08 ± 1.12 µM), also showing good drug-like properties according to the absorption, Distribution, Metabolism, Excretion, Toxicity  analysis.
  
  
  CONCLUSIONS
  A new family of non-hepatotoxic permeable tacrine analogs, showing selective butyrylcholinesterase inhibition, have been discovered for the potential treatment of Alzheimer's disease.
authors.affiliation: Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et Polymères Faculté des Sciences de Sfax, Université de Sfax, 3018 Sfax, Tunisia.
authors.forename: Oussama
authors.initials: O
authors.lastname: Cherif
authors.forename: Fatma
authors.initials: F
authors.lastname: Allouche
authors.forename: Fakher
authors.initials: F
authors.lastname: Chabchoub
authors.forename: Mourad
authors.initials: M
authors.lastname: Chioua
authors.forename: Elena
authors.initials: E
authors.lastname: Soriano
authors.forename: Matilde
authors.initials: M
authors.lastname: Yañez
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.forename: Jose
authors.initials: J
authors.lastname: Marco-Contelles
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013619:Tacrine / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D007555:Isoxazoles; D011994:Recombinant Proteins; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase