Details

Autor(en) / Beteiligte

• Dias, Kris Simone T.
• de Paula, Cynthia T.
• dos Santos, Thiago
• Souza, Isis N.O.
• Boni, Marina S.
• Guimarães, Marcos J.R.
• da Silva, Fernanda M.R.
• Castro, Newton G.
• Neves, Gilda A.
• Veloso, Clarice C.
• Coelho, Márcio M.
• de Melo, Ivo Souza F.
• Giusti, Fabiana C.V.
• Giusti-Paiva, Alexandre
• da Silva, Marcelo L.
• Dardenne, Laurent E.
• Guedes, Isabella A.
• Pruccoli, Letizia
• Morroni, Fabiana
• Tarozzi, Andrea
• Viegas, Claudio

Titel

Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease

Ist Teil von

• European journal of medicinal chemistry, 2017-04, Vol.130, p.440-457

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2017

Quelle

ScienceDirect

Beschreibungen/Notizen

• A novel series of feruloyl-donepezil hybrid compounds were designed, synthesized and evaluated as multitarget drug candidates for the treatment of Alzheimer's Disease (AD). In vitro results revealed potent acetylcholinesterase (AChE) inhibitory activity for some of these compounds and all of them showed moderate antioxidant properties. Compounds 12a, 12b and 12c were the most potent AChE inhibitors, highlighting 12a with IC50 = 0.46 μM. In addition, these three most promising compounds exhibited significant in vivo anti-inflammatory activity in the mice paw edema, pleurisy and formalin-induced hyperalgesy models, in vitro metal chelator activity for Cu2+ and Fe2+, and neuroprotection of human neuronal cells against oxidative damage. Molecular docking studies corroborated the in vitro inhibitory mode of interaction of these active compounds on AChE. Based on these data, compound 12a was identified as a novel promising drug prototype candidate for the treatment of AD with innovative structural feature and multitarget effects. [Display omitted] •Novel donepezil-feruloyl hybrids were synthesized as MTDL for AD.•Compounds 12a, 12b and 12c showed the highest inhibitory activities for EeAChE.•Compound 12a showed IC50 = 0.46 μM of inhibition AChE.•Compound 12a shows multiple effects consistent with the aimed multi-target directed profile.