title: Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease.
abstract: In this work we describe the synthesis and biological evaluation of the tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are the result of the juxtaposition of an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) and a 1,4-DHP such as nimodipine (2). Compounds 3-11 are very selective and potent AChEIs and show an excellent neuroprotective profile and a moderate Ca2+ channel blockade effect. Consequently, these molecules are new potential drugs for the treatment of Alzheimer's disease.
authors.affiliation: Laboratorio de Radicales Libres (IQOG, CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain. iqoc21@iqog.csic.es
authors.forename: José
authors.initials: J
authors.lastname: Marco-Contelles
authors.forename: Rafael
authors.initials: R
authors.lastname: León
authors.forename: Cristóbal
authors.initials: C
authors.lastname: de Los Ríos
authors.forename: Antonio
authors.initials: A
authors.lastname: Guglietta
authors.forename: José
authors.initials: J
authors.lastname: Terencio
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villarroya
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000737:chemistry*; D004524:Eels / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D015220:Calcium Channels; D004095:Dihydropyridines; D018696:Neuroprotective Agents; D013619:Tacrine; C038806:1,4-dihydropyridine; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase; D002118:Calcium