Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers

Detalhes bibliográficos
Autor(a) principal: Bosquesi, Priscila Longhin [UNESP]
Data de Publicação: 2020
Outros Autores: Melchior, Aylime Castanho Bolognesi [UNESP], Pavan, Aline Renata [UNESP], Lanaro, Carolina, de Souza, Cristiane Maria, Rusinova, Radda, Chelucci, Rafael Consolin [UNESP], Barbieri, Karina Pereira [UNESP], Fernandes, Guilherme Felipe dos Santos [UNESP], Carlos, Iracilda Zepone [UNESP], Andersen, Olaf Sparre, Costa, Fernando Ferreira, Dos Santos, Jean Leandro [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.bioorg.2020.103948
http://hdl.handle.net/11449/198853
Resumo: Resveratrol (RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1–64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + γA), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.
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spelling Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducersEpigeneticFetal hemoglobin inducersGamma-globin inducersNitric oxideResveratrolSickle Cell DiseaseResveratrol (RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1–64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + γA), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Optical SocietyUniversidade Estadual PaulistaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institutes of HealthSão Paulo State University (UNESP) School of Pharmaceutical SciencesUniversity of Campinas (UNICAMP) Hematology and Hemotherapy CenterWeill Cornell Medical College Department of Physiology and BiophysicsSão Paulo State University (UNESP) School of Pharmaceutical SciencesFAPESP: 2012/50359-2FAPESP: 2014/00984-3CNPq: 304731/2017-0National Institutes of Health: GM21342Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Weill Cornell Medical CollegeBosquesi, Priscila Longhin [UNESP]Melchior, Aylime Castanho Bolognesi [UNESP]Pavan, Aline Renata [UNESP]Lanaro, Carolinade Souza, Cristiane MariaRusinova, RaddaChelucci, Rafael Consolin [UNESP]Barbieri, Karina Pereira [UNESP]Fernandes, Guilherme Felipe dos Santos [UNESP]Carlos, Iracilda Zepone [UNESP]Andersen, Olaf SparreCosta, Fernando FerreiraDos Santos, Jean Leandro [UNESP]2020-12-12T01:23:41Z2020-12-12T01:23:41Z2020-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.bioorg.2020.103948Bioorganic Chemistry, v. 100.1090-21200045-2068http://hdl.handle.net/11449/19885310.1016/j.bioorg.2020.1039482-s2.0-85084977756Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBioorganic Chemistryinfo:eu-repo/semantics/openAccess2021-10-22T20:42:42Zoai:repositorio.unesp.br:11449/198853Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:42:48.451324Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
title Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
spellingShingle Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
Bosquesi, Priscila Longhin [UNESP]
Epigenetic
Fetal hemoglobin inducers
Gamma-globin inducers
Nitric oxide
Resveratrol
Sickle Cell Disease
title_short Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
title_full Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
title_fullStr Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
title_full_unstemmed Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
title_sort Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers
author Bosquesi, Priscila Longhin [UNESP]
author_facet Bosquesi, Priscila Longhin [UNESP]
Melchior, Aylime Castanho Bolognesi [UNESP]
Pavan, Aline Renata [UNESP]
Lanaro, Carolina
de Souza, Cristiane Maria
Rusinova, Radda
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Fernandes, Guilherme Felipe dos Santos [UNESP]
Carlos, Iracilda Zepone [UNESP]
Andersen, Olaf Sparre
Costa, Fernando Ferreira
Dos Santos, Jean Leandro [UNESP]
author_role author
author2 Melchior, Aylime Castanho Bolognesi [UNESP]
Pavan, Aline Renata [UNESP]
Lanaro, Carolina
de Souza, Cristiane Maria
Rusinova, Radda
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Fernandes, Guilherme Felipe dos Santos [UNESP]
Carlos, Iracilda Zepone [UNESP]
Andersen, Olaf Sparre
Costa, Fernando Ferreira
Dos Santos, Jean Leandro [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade Estadual de Campinas (UNICAMP)
Weill Cornell Medical College
dc.contributor.author.fl_str_mv Bosquesi, Priscila Longhin [UNESP]
Melchior, Aylime Castanho Bolognesi [UNESP]
Pavan, Aline Renata [UNESP]
Lanaro, Carolina
de Souza, Cristiane Maria
Rusinova, Radda
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Fernandes, Guilherme Felipe dos Santos [UNESP]
Carlos, Iracilda Zepone [UNESP]
Andersen, Olaf Sparre
Costa, Fernando Ferreira
Dos Santos, Jean Leandro [UNESP]
dc.subject.por.fl_str_mv Epigenetic
Fetal hemoglobin inducers
Gamma-globin inducers
Nitric oxide
Resveratrol
Sickle Cell Disease
topic Epigenetic
Fetal hemoglobin inducers
Gamma-globin inducers
Nitric oxide
Resveratrol
Sickle Cell Disease
description Resveratrol (RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1–64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + γA), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-12T01:23:41Z
2020-12-12T01:23:41Z
2020-07-01
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/10.1016/j.bioorg.2020.103948
Bioorganic Chemistry, v. 100.
1090-2120
0045-2068
http://hdl.handle.net/11449/198853
10.1016/j.bioorg.2020.103948
2-s2.0-85084977756
url http://dx.doi.org/10.1016/j.bioorg.2020.103948
http://hdl.handle.net/11449/198853
identifier_str_mv Bioorganic Chemistry, v. 100.
1090-2120
0045-2068
10.1016/j.bioorg.2020.103948
2-s2.0-85084977756
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Bioorganic Chemistry
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
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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