AUTHOR=Marco-Contelles José , Unzeta Mercedes , Bolea Irene , Esteban Gerard , Ramsay Rona R. , Romero Alejandro , Martínez-Murillo Ricard , Carreiras M. Carmo , Ismaili Lhassane TITLE=ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy JOURNAL=Frontiers in Neuroscience VOLUME=10 YEAR=2016 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00294 DOI=10.3389/fnins.2016.00294 ISSN=1662-453X ABSTRACT=

Highlights:

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 enzymes

ASS2324 shows antioxidant, neuroprotective and suitable permeability properties

ASS2324 restores the scopolamine-induced cognitive impairment to the same extent as donepezil, and is less toxic

ASS2324 prevents β-amyloid induced aggregation in the cortex of double transgenic mice

ASS2324 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.