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.

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