Multifunctional Small Molecules as Potential Anti-Alzheimer’s Disease Agents |
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Authors: | Beatrice Bargagna Lidia Ciccone Susanna Nencetti M Amlia Santos Sílvia Chaves Caterina Camodeca Elisabetta Orlandini |
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Institution: | 1.Department of Earth Sciences, University of Pisa, Via Santa Maria 53-55, 56100 Pisa, Italy;2.Centro de Química Estrutural and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal;3.Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (L.C.); (S.N.); (C.C.);4.Research Center “E. Piaggio”, University of Pisa, 56122 Pisa, Italy |
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Abstract: | Alzheimer’s disease (AD) is a severe multifactorial neurodegenerative disorder characterized by a progressive loss of neurons in the brain. Despite research efforts, the pathogenesis and mechanism of AD progression are not yet completely understood. There are only a few symptomatic drugs approved for the treatment of AD. The multifactorial character of AD suggests that it is important to develop molecules able to target the numerous pathological mechanisms associated with the disease. Thus, in the context of the worldwide recognized interest of multifunctional ligand therapy, we report herein the synthesis, characterization, physicochemical and biological evaluation of a set of five (1a–e) new ferulic acid-based hybrid compounds, namely feroyl-benzyloxyamidic derivatives enclosing different substituent groups, as potential anti-Alzheimer’s disease agents. These hybrids can keep both the radical scavenging activity and metal chelation capacity of the naturally occurring ferulic acid scaffold, presenting also good/mild capacity for inhibition of self-Aβ aggregation and fairly good inhibition of Cu-induced Aβ aggregation. The predicted pharmacokinetic properties point towards good absorption, comparable to known oral drugs. |
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Keywords: | Alzheimer’ s disease (AD) multifunctional drugs metal chelation antioxidant activity Aβ stabilizers neurodegeneration ferulic acid multitarget drugs |
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