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Highlights:ASS2324  is a hybrid compound resulting from the juxtaposition of donepezil and the propargylamine  PF9601NASS2324  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 laboratoriesThe 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.

ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy