title: Synthesis and biological evaluation of tacrine-thiadiazolidinone hybrids as dual acetylcholinesterase inhibitors.
abstract: The synthesis of tacrine-thiadiazolidinone hybrids is described. These compounds are designed as dual acetylcholinesterase inhibitors binding simultaneously to the peripheral and catalytic sites of the enzyme. All tested compounds exhibit significant AChE inhibitory activity. Competition assays using propidium as reference of selective ligand for the peripheral anionic site on acetylcholinesterase indicates the influence of the designed compounds over the peripheral site. They can be considered as new leads in the optimization of Alzheimer's disease modifying agents.
authors.affiliation: Neuropharma, S.A. Avda. de la Industria 52, Tres Cantos, 28760 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dorronsoro
authors.forename: Diana
authors.initials: D
authors.lastname: Alonso
authors.forename: Ana
authors.initials: A
authors.lastname: Castro
authors.forename: Maria
authors.initials: M
authors.lastname: del Monte
authors.forename: Esther
authors.initials: E
authors.lastname: García-Palomero
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D011419:Propidium / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D013830:Thiadiazoles; D011419:Propidium; D013619:Tacrine; D000110:Acetylcholinesterase