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2014-03-27

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/54947

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

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Recurs relacionat

http://dx.doi.org/10.1021/jm401824w

Resum

We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Matèries

Compostos orgànics, Disseny de medicaments, Inhibidors enzimàtics, Malaltia d'Alzheimer, Quimioteràpia

Matèries (anglès)

Organic compounds, Drug design, Enzyme inhibitors, Alzheimer's disease, Chemotherapy

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Col·leccions

Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

VIAYNA, Elisabet, SOLA, Irene, BARTOLINI, Manuela, DE SIMONE, Angela, TAPIA-ROJAS, Cheril, SERRANO, Felipe g., SABATÉ LAGUNAS, Raimon, JUÁREZ-JIMÉNEZ, Jordi, PÉREZ FERNÁNDEZ, Belén, LUQUE GARRIGA, F. xavier, ANDRISANO, Vincenza, CLOS, Victòria, INESTROSA, Nibaldo c., MUÑOZ-TORRERO LÓPEZ-IBARRA, Diego. Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. _Journal of Medicinal Chemistry_. 2014. Vol. 57, núm. 6, pàgs. 2549-2567. [consulta: 28 de gener de 2026]. ISSN: 0022-2623. [Disponible a: https://hdl.handle.net/2445/54947]

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