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. 2016 Jun 28:10:294.
doi: 10.3389/fnins.2016.00294. eCollection 2016.

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

José Marco-Contelles  1 , Mercedes Unzeta  2 , Irene Bolea  2 , Gerard Esteban  2 , Rona R Ramsay  3 , Alejandro Romero  4 , Ricard Martínez-Murillo  5 , M Carmo Carreiras  6 , Lhassane Ismaili  7
Affiliations

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

José Marco-Contelles et al. Front Neurosci. .

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.

Keywords: Alzheimer's disease; cholinesterases; drugs; monoamine oxidases; multi-target directed ligands.

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Figures

Figure 1
Figure 1
Structure of compounds donepezil, PF9601N, ASS234, and JMC1-4.
Figure 2
Figure 2
Structure and IC50 values for the inhibition of ChEs and MAO enzymes by ASS234.
See this image and copyright information in PMC

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