Novel benzylidenephenylpyrrolizinones with pleiotropic activities potentially useful in Alzheimer's disease treatment

• Novel benzylidenephenylpyrrolizinones were synthesized.
• Some of them acted as antioxidant, metal chelating and amyloid aggregation inhibitors.
• Benzylidenephenylpyrrolizinones appeared devoid of cytotoxicity.
• They further possess good predictive druggability parameters.

This work describes the synthesis and the biological evaluation of novel benzylidenephenylpyrrolizinones as potential antioxidant, metal chelating or amyloid β (βA) aggregation inhibitors. Some derivatives exhibited interesting results in regard to several of the performed evaluations and appear as valuable Multi-Target Directed Ligands with potential therapeutic interest in Alzheimer's disease. Among them, compound 29 particularly appears as a valuable radical and NO scavenger, a Cu(II) and Fe(II) chelating agent and exhibits moderate βA aggregation inhibition properties. These activities, associated to a good predictive bioavailability and a lack of cytotoxicity, design it as a promising hit for further in vivo investigation.

Figure optionsDownload as PowerPoint slide