Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-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...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/14/3165 |
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| author | Matheus de Freitas Silva Ellen Tardelli Lima Letizia Pruccoli Newton G. Castro Marcos Jorge R. Guimarães Fernanda M. R. da Silva Nathalia Fonseca Nadur Luciana Luiz de Azevedo Arthur Eugen Kümmerle Isabella Alvim Guedes Laurent Emmanuel Dardenne Vanessa Silva Gontijo Andrea Tarozzi Claudio Viegas |
| author_facet | Matheus de Freitas Silva Ellen Tardelli Lima Letizia Pruccoli Newton G. Castro Marcos Jorge R. Guimarães Fernanda M. R. da Silva Nathalia Fonseca Nadur Luciana Luiz de Azevedo Arthur Eugen Kümmerle Isabella Alvim Guedes Laurent Emmanuel Dardenne Vanessa Silva Gontijo Andrea Tarozzi Claudio Viegas |
| author_sort | Matheus de Freitas Silva |
| collection | DOAJ |
| description | 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 <i>N</i>-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative <b>3e</b> showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ<sub>42</sub> oligomers in neuronal SH-SY5Y cells. In parallel, compound <b>3e</b> showed a good profile of safety and ADME parameters. Taken together, these results suggest that <b>3e</b> could be considered a lead compound for the further development of AD therapeutics. |
| first_indexed | 2024-03-10T18:32:40Z |
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| id | doaj.art-766736aee49e4dc6b5abdcf74046e349 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:32:40Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-766736aee49e4dc6b5abdcf74046e3492023-11-20T06:28:01ZengMDPI AGMolecules1420-30492020-07-012514316510.3390/molecules25143165Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s DiseaseMatheus de Freitas Silva0Ellen Tardelli Lima1Letizia Pruccoli2Newton G. Castro3Marcos Jorge R. Guimarães4Fernanda M. R. da Silva5Nathalia Fonseca Nadur6Luciana Luiz de Azevedo7Arthur Eugen Kümmerle8Isabella Alvim Guedes9Laurent Emmanuel Dardenne10Vanessa Silva Gontijo11Andrea Tarozzi12Claudio Viegas13Laboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Jovino Fernandes Sales Avenue, 2600, Alfenas 37130000, MG, BrazilLaboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Jovino Fernandes Sales Avenue, 2600, Alfenas 37130000, MG, BrazilDepartment for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyLaboratory of Molecular Pharmacology, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Rio de Janeiro 21941590, RJ, BrazilLaboratory of Molecular Pharmacology, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Rio de Janeiro 21941590, RJ, BrazilLaboratory of Molecular Pharmacology, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Rio de Janeiro 21941590, RJ, BrazilLaboratory of Molecular Diversity and Medicinal Chemistry (LaDMol-QM), Federal Rural University of Rio de Janeiro—UFRRJ, BR-465, Km 7 Seropédica-Rio de Janeiro 23890000, RJ, BrazilLaboratory of Molecular Diversity and Medicinal Chemistry (LaDMol-QM), Federal Rural University of Rio de Janeiro—UFRRJ, BR-465, Km 7 Seropédica-Rio de Janeiro 23890000, RJ, BrazilLaboratory of Molecular Diversity and Medicinal Chemistry (LaDMol-QM), Federal Rural University of Rio de Janeiro—UFRRJ, BR-465, Km 7 Seropédica-Rio de Janeiro 23890000, RJ, BrazilGrupo de Modelagem Molecular em Sistemas Biológicos (GMMSB), National Laboratory for Scientific Computing—LNCC, Avenida Getúlio Vargas, 333, Petrópolis 25651-076, RJ, BrazilGrupo de Modelagem Molecular em Sistemas Biológicos (GMMSB), National Laboratory for Scientific Computing—LNCC, Avenida Getúlio Vargas, 333, Petrópolis 25651-076, RJ, BrazilLaboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Jovino Fernandes Sales Avenue, 2600, Alfenas 37130000, MG, BrazilDepartment for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyLaboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Jovino Fernandes Sales Avenue, 2600, Alfenas 37130000, MG, BrazilAlzheimer’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 <i>N</i>-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative <b>3e</b> showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ<sub>42</sub> oligomers in neuronal SH-SY5Y cells. In parallel, compound <b>3e</b> showed a good profile of safety and ADME parameters. Taken together, these results suggest that <b>3e</b> could be considered a lead compound for the further development of AD therapeutics.https://www.mdpi.com/1420-3049/25/14/3165molecular hybridizationAlzheimer’s diseasecurcuminresveratrol |
| spellingShingle | Matheus de Freitas Silva Ellen Tardelli Lima Letizia Pruccoli Newton G. Castro Marcos Jorge R. Guimarães Fernanda M. R. da Silva Nathalia Fonseca Nadur Luciana Luiz de Azevedo Arthur Eugen Kümmerle Isabella Alvim Guedes Laurent Emmanuel Dardenne Vanessa Silva Gontijo Andrea Tarozzi Claudio Viegas Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease Molecules molecular hybridization Alzheimer’s disease curcumin resveratrol |
| title | Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease |
| title_full | Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease |
| title_fullStr | Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease |
| title_short | Design, Synthesis and Biological Evaluation of Novel Triazole <em>N</em>-acylhydrazone Hybrids for Alzheimer’s Disease |
| title_sort | design synthesis and biological evaluation of novel triazole em n em acylhydrazone hybrids for alzheimer s disease |
| topic | molecular hybridization Alzheimer’s disease curcumin resveratrol |
| url | https://www.mdpi.com/1420-3049/25/14/3165 |
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