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

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Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniv Birmingham-
Autor(es): dc.creatorZazeri, Gabriel [UNESP]-
Autor(es): dc.creatorPovinelli, Ana Paula R. [UNESP]-
Autor(es): dc.creatorLe Duff, Cecile S.-
Autor(es): dc.creatorTang, Bridget-
Autor(es): dc.creatorCornelio, Marinonio L. [UNESP]-
Autor(es): dc.creatorJones, Alan M.-
Data de aceite: dc.date.accessioned2022-02-22T00:11:19Z-
Data de disponibilização: dc.date.available2022-02-22T00:11:19Z-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-06-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/molecules25122841-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/197119-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/197119-
Descrição: dc.descriptionInspired 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.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionMolecules, MDPI-
Descrição: dc.descriptionIBILCE, Dept Fisica, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil-
Descrição: dc.descriptionUniv Birmingham, Sch Pharm, Edgbaston B15 2TT, England-
Descrição: dc.descriptionUniv Birmingham, Sch Chem, Edgbaston B15 2TT, England-
Descrição: dc.descriptionIBILCE, Dept Fisica, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil-
Descrição: dc.descriptionCAPES: 001-
Formato: dc.format17-
Idioma: dc.languageen-
Publicador: dc.publisherMdpi-
Relação: dc.relationMolecules-
???dc.source???: dc.sourceWeb of Science-
Palavras-chave: dc.subjectmolecular docking-
Palavras-chave: dc.subjectpiperine-
Palavras-chave: dc.subjectpiperlongumine-
Título: dc.titleSynthesis and Spectroscopic Analysis of Piperine- and Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1 beta and NF-kappa B Proteins-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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