title: Multitarget compounds bearing tacrine- and donepezil-like structural and functional motifs for the potential treatment of Alzheimer's disease.
abstract: Alzheimer's disease is a multifactorial and fatal neurodegenerative disorder characterized by decline of cholinergic function, deregulation of other neurotransmitter systems, β-amyloid fibril deposition, and β-amyloid oligomers formation. Based on the involvement of a relevant number of biological systems in Alzheimer's disease progression, multitarget compounds may enable therapeutic efficacy. Accordingly, compounds possessing, besides anticholinergic activity and β-amyloid aggregation inhibition properties, metal chelating and/or nitric oxide releasing properties with additional antioxidant capacity were developed. Other targets relevant to Alzheimer's disease have also been considered in the last years for producing multitarget compounds such as β-secretase, monoamino oxidases, serotonin receptors and sigma 1 receptors. The purpose of this review will be to highlight recent reports on the development of multitarget compounds for Alzheimer's disease published within the last years focusing on multifunctional ligands characterized by tacrine-like and donepezil-like structures.
authors.affiliation: Neurosciences Intégratives et Cliniques EA 481, Laboratoire de Chimie Organique et Thérapeutique, UFR SMP, 19 rue Ambroise Paré, Université de Franche-Comté, Université Bourgogne Franche-Comté, CHRU Besançon, F-25000 Besançon, France. Electronic address: lhassane.ismaili@univ-fcomte.fr.
authors.forename: Lhassane
authors.initials: L
authors.lastname: Ismaili
authors.affiliation: Neurosciences Intégratives et Cliniques EA 481, Laboratoire de Chimie Organique et Thérapeutique, UFR SMP, 19 rue Ambroise Paré, Université de Franche-Comté, Université Bourgogne Franche-Comté, CHRU Besançon, F-25000 Besançon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Refouvelet
authors.affiliation: Neurosciences Intégratives et Cliniques EA 481, Laboratoire de Chimie Organique et Thérapeutique, UFR SMP, 19 rue Ambroise Paré, Université de Franche-Comté, Université Bourgogne Franche-Comté, CHRU Besançon, F-25000 Besançon, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benchekroun
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry and Pharmacy, Università di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Brogi
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry and Pharmacy, Università di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry and Pharmacy, Università di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry and Pharmacy, Università di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.affiliation: Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Filipic
authors.affiliation: Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Danica
authors.initials: D
authors.lastname: Agbaba
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Esteban
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Unzeta
authors.affiliation: Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia. Electronic address: knikolic@pharmacy.bg.ac.rs.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nikolic
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry and Pharmacy, Università di Siena, Via A. Moro, 53100 Siena, Italy. Electronic address: butini3@unisi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.affiliation: Laboratory of Medicinal Chemistry (IQOG, CSIC), C/ Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: iqoc21@iqog.csic.es.
authors.forename: José
authors.initials: J
authors.lastname: Marco-Contelles
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000627:therapeutic use*; D008024:Ligands; D010880:Piperidines / Q000737:chemistry / Q000627:therapeutic use*; D013619:Tacrine / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D008024:Ligands; D010880:Piperidines; D013619:Tacrine; D000077265:Donepezil
keywords: Acetylcholinesterase; Alzheimer's disease; Beta secretase; Butyrylcholinesterase; Cholinesterases; Histamine receptor; Monoamine oxidases; Multi-target-directed ligand; Nitric oxide; Reactive oxygen species; Serotonin receptors; β-Amyloid