Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer's Disease

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics

Comentarios a una sentencia anunciada : el proceso Lula

El centenar de textos que conforman este libro -escritos por un movimiento de prestigiosos/as juristas y abogados- desgranan el procedimiento al que fue sometido Lula. En la opinión de las y los autores de los artículos las normas no fueron observadas, y su inobservancia llevó a que se dictaminase una decisión injusta. Frases del estilo "Voy a tomar una decisión revolucionaria, dejando de lado la ley, porque por la ley no se puede condenarlo de ninguna manera”, dichas en los juicios por las más altas autoridades judiciales militares y civiles, hoy son conocidas gracias a quienes se abocaron al trabajo de escuchar los audios de aquellas sesiones, nutriendo las reflexiones que argumentan sobre el imperativo de la hora: restablecer el estado de derecho y absolver al presidente Lula Da Silva

Comentários a uma sentença anunciada : o processo Lula

“Comentários a uma sentença: o Caso Lula” é talvez o mais importante documento jurídico publicado no Brasil em décadas. A presente coletânea de artigos nasceu de um movimento espontâneo e bastante significativo de juristas brasileiros e estrangeiros que examinaram cuidadosamente a sentença proferida no âmbito do processo que tramitou na 13ª Vara Federal de Curitiba, no caso que ficou conhecido na mídia como o do “tríplex do Guarujá”. <br>De la presentación de Geraldo Prad