Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/molecules25122841 http://hdl.handle.net/11449/197119 |
Resumo: | Inspired by the remarkable bioactivities exhibited by the natural products, piperine and piperlongumine, we synthesised eight natural product-inspired analogues to further investigate their structures. For the first time, we confirmed the structure of the key cyclised dihydropyrazolecarbothioamide piperine analogues including the use of two-dimensional (2D) N-15-based spectroscopy nuclear magnetic resonance (NMR) spectroscopy. Prior investigations demonstrated promising results from these scaffolds for the inhibition of inflammatory response via downregulation of the IL-1 beta and NF-kappa B pathway. However, the molecular interaction of these molecules with their protein targets remains unknown. Ab initio calculations revealed the electronic density function map of the molecules, showing the effects of structural modification in the electronic structure. Finally, molecular interactions between the synthesized molecules and the proteins IL-1 beta and NF-kappa B were achieved. Docking results showed that all the analogues interact in the DNA binding site of NF-kappa B with higher affinity compared to the natural products and, with the exception of9aand9b,have higher affinity than the natural products for the binding site of IL-1 beta. Specificity for the molecular recognition of 3a,3c and 9b with IL-1 beta through cation-pi interactions was determined. These results revealed 3a, 3c, 4a, 4c and 10 as the most promising molecules to be evaluated as IL-1 beta and NF-kappa B inhibitors. |
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Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteinsmolecular dockingpiperinepiperlongumineInspired by the remarkable bioactivities exhibited by the natural products, piperine and piperlongumine, we synthesised eight natural product-inspired analogues to further investigate their structures. For the first time, we confirmed the structure of the key cyclised dihydropyrazolecarbothioamide piperine analogues including the use of two-dimensional (2D) N-15-based spectroscopy nuclear magnetic resonance (NMR) spectroscopy. Prior investigations demonstrated promising results from these scaffolds for the inhibition of inflammatory response via downregulation of the IL-1 beta and NF-kappa B pathway. However, the molecular interaction of these molecules with their protein targets remains unknown. Ab initio calculations revealed the electronic density function map of the molecules, showing the effects of structural modification in the electronic structure. Finally, molecular interactions between the synthesized molecules and the proteins IL-1 beta and NF-kappa B were achieved. Docking results showed that all the analogues interact in the DNA binding site of NF-kappa B with higher affinity compared to the natural products and, with the exception of9aand9b,have higher affinity than the natural products for the binding site of IL-1 beta. Specificity for the molecular recognition of 3a,3c and 9b with IL-1 beta through cation-pi interactions was determined. These results revealed 3a, 3c, 4a, 4c and 10 as the most promising molecules to be evaluated as IL-1 beta and NF-kappa B inhibitors.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Molecules, MDPIIBILCE, Dept Fisica, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilUniv Birmingham, Sch Pharm, Edgbaston B15 2TT, EnglandUniv Birmingham, Sch Chem, Edgbaston B15 2TT, EnglandIBILCE, Dept Fisica, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilCAPES: 001MdpiUniversidade Estadual Paulista (Unesp)Univ BirminghamZazeri, Gabriel [UNESP]Povinelli, Ana Paula R. [UNESP]Le Duff, Cecile S.Tang, BridgetCornelio, Marinonio L. [UNESP]Jones, Alan M.2020-12-10T20:06:45Z2020-12-10T20:06:45Z2020-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17http://dx.doi.org/10.3390/molecules25122841Molecules. Basel: Mdpi, v. 25, n. 12, 17 p., 2020.http://hdl.handle.net/11449/19711910.3390/molecules25122841WOS:000553601100001Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMoleculesinfo:eu-repo/semantics/openAccess2021-10-23T11:51:35Zoai:repositorio.unesp.br:11449/197119Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:48:58.533614Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
title |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
spellingShingle |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins Zazeri, Gabriel [UNESP] molecular docking piperine piperlongumine |
title_short |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
title_full |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
title_fullStr |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
title_full_unstemmed |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
title_sort |
Synthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins |
author |
Zazeri, Gabriel [UNESP] |
author_facet |
Zazeri, Gabriel [UNESP] Povinelli, Ana Paula R. [UNESP] Le Duff, Cecile S. Tang, Bridget Cornelio, Marinonio L. [UNESP] Jones, Alan M. |
author_role |
author |
author2 |
Povinelli, Ana Paula R. [UNESP] Le Duff, Cecile S. Tang, Bridget Cornelio, Marinonio L. [UNESP] Jones, Alan M. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Univ Birmingham |
dc.contributor.author.fl_str_mv |
Zazeri, Gabriel [UNESP] Povinelli, Ana Paula R. [UNESP] Le Duff, Cecile S. Tang, Bridget Cornelio, Marinonio L. [UNESP] Jones, Alan M. |
dc.subject.por.fl_str_mv |
molecular docking piperine piperlongumine |
topic |
molecular docking piperine piperlongumine |
description |
Inspired by the remarkable bioactivities exhibited by the natural products, piperine and piperlongumine, we synthesised eight natural product-inspired analogues to further investigate their structures. For the first time, we confirmed the structure of the key cyclised dihydropyrazolecarbothioamide piperine analogues including the use of two-dimensional (2D) N-15-based spectroscopy nuclear magnetic resonance (NMR) spectroscopy. Prior investigations demonstrated promising results from these scaffolds for the inhibition of inflammatory response via downregulation of the IL-1 beta and NF-kappa B pathway. However, the molecular interaction of these molecules with their protein targets remains unknown. Ab initio calculations revealed the electronic density function map of the molecules, showing the effects of structural modification in the electronic structure. Finally, molecular interactions between the synthesized molecules and the proteins IL-1 beta and NF-kappa B were achieved. Docking results showed that all the analogues interact in the DNA binding site of NF-kappa B with higher affinity compared to the natural products and, with the exception of9aand9b,have higher affinity than the natural products for the binding site of IL-1 beta. Specificity for the molecular recognition of 3a,3c and 9b with IL-1 beta through cation-pi interactions was determined. These results revealed 3a, 3c, 4a, 4c and 10 as the most promising molecules to be evaluated as IL-1 beta and NF-kappa B inhibitors. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-10T20:06:45Z 2020-12-10T20:06:45Z 2020-06-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/molecules25122841 Molecules. Basel: Mdpi, v. 25, n. 12, 17 p., 2020. http://hdl.handle.net/11449/197119 10.3390/molecules25122841 WOS:000553601100001 |
url |
http://dx.doi.org/10.3390/molecules25122841 http://hdl.handle.net/11449/197119 |
identifier_str_mv |
Molecules. Basel: Mdpi, v. 25, n. 12, 17 p., 2020. 10.3390/molecules25122841 WOS:000553601100001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecules |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
17 |
dc.publisher.none.fl_str_mv |
Mdpi |
publisher.none.fl_str_mv |
Mdpi |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129465006424064 |