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2-Arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying agents
The complex etiology of Alzheimer's disease prompts scientists to develop multi-target strategies to combat causes and symptoms. In line with this modern paradigm and as a follow-up to our previous studies, we designed and synthesized a focused collection of new 2-arylbenzofurans and evaluated...
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Published in: | European journal of medicinal chemistry 2012-12, Vol.58, p.519-532 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The complex etiology of Alzheimer's disease prompts scientists to develop multi-target strategies to combat causes and symptoms. In line with this modern paradigm and as a follow-up to our previous studies, we designed and synthesized a focused collection of new 2-arylbenzofurans and evaluated their biological properties towards specific targets involved in AD, namely human AChE and human BuChE, and Aβ fibril formation. Selected compounds were also tested for their ability to inhibit Aβ neurotoxicity in terms of neuronal viability loss, and to prevent Aβ peptide-binding to cell membrane and intracellular reactive oxygen species (ROS) formation. The different modifications introduced in the structure of our lead compound led to an increase in activity towards one or more of the selected targets: the anticholinesterase activity of some compounds was found to be significantly higher than previously obtained related molecules, and the compounds also proved to possess Aβ anti-aggregating properties and neuroprotective effects. The most interesting multi-target compounds were 18, and 1. Interestingly, 1 also showed good selectivity and moderate affinity for CB1 receptor, opening new perspectives in the field of research on AD, since cannabinoid ligands have been widely reported to have neuroprotective properties.
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► A focused collection of new 2-arylbenzofurans were designed and synthesized. ► The biological profile towards cholinesterases and Aβ-aggregation was evaluated. ► Selected compounds were also tested for their ability to inhibit Aβ neurotoxicity. ► The most interesting multi-target compounds were 18 and 1. ► 1 also showed good selectivity and moderate affinity for CB1 receptor. |
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2012.10.045 |