title: ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy.
abstract: ASS2324 is a hybrid compound resulting from the juxtaposition of donepezil and the propargylamine PF9601N ASS2324 is a multi-target directed propargylamine able to bind to all the AChE/BuChE and MAO A/B enzymesASS2324 shows antioxidant, neuroprotective and suitable permeability propertiesASS2324 restores the scopolamine-induced cognitive impairment to the same extent as donepezil, and is less toxicASS2324 prevents β-amyloid induced aggregation in the cortex of double transgenic miceASS2324 is the most advanced anti-Alzheimer agent for pre-clinical studies that we have identified in our laboratories The complex nature of Alzheimer's disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines (MTDP) showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase (MAO) inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aβ-aggregation, and possessing antioxidant and neuroprotective properties.
authors.affiliation: Laboratory of Medicinal Chemistry, Institute of General Organic Chemistry, Cajal Institute (CSIC) Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Marco-Contelles
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Unzeta
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Bolea
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut de Neurociències, Universitat Autònoma de Barcelona Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Esteban
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews St Andrews, UK.
authors.forename: Rona R
authors.initials: RR
authors.lastname: Ramsay
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Complutense University of Madrid Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.affiliation: Neurovascular Research Group, Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute (CSIC) Madrid, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Martínez-Murillo
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon Lisbon, Portugal.
authors.forename: M Carmo
authors.initials: MC
authors.lastname: Carreiras
authors.affiliation: Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques EA 481, Université Franche-Comté, Université Bourgogne Franche-Comté, UFR SMP Besançon, France.
authors.forename: Lhassane
authors.initials: L
authors.lastname: Ismaili
keywords: Alzheimer's disease; cholinesterases; drugs; monoamine oxidases; multi-target directed ligands