A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.exphem.2017.10.003 http://hdl.handle.net/11449/170441 |
Resumo: | Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties. |
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Repositório Institucional da UNESP |
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spelling |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytesFetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.Hematology and Hemotherapy Center, University of Campinas-UNICAMP, Campinas, BrazilDepartment of Clinical Pathology, School of Medicine, University of Campinas-UNICAMP, Campinas, BrazilSão Paulo State University (UNESP), School of Pharmaceutical Science, Araraquara, BrazilDepartment of Anesthesiology and Perioperative Medicine, Augusta University, Augusta, GA, USADepartment of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USAUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Lanaro, CarolinaFranco-Penteado, Carla F.Silva, Fabio H.Fertrin, Kleber Y.dos Santos, Jean LeandroWade, MarleneYerigenahally, Shobhade Melo, Thais R.Chin, Chung ManKutlar, AbdullahMeiler, Steffen E.Costa, Fernando Ferreira2018-12-11T16:50:49Z2018-12-11T16:50:49Z2017-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.exphem.2017.10.003Experimental Hematology.1873-23990301-472Xhttp://hdl.handle.net/11449/17044110.1016/j.exphem.2017.10.0032-s2.0-850366472412-s2.0-85036647241.pdf97343336079754130000-0003-4141-0455Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengExperimental Hematologyinfo:eu-repo/semantics/openAccess2023-12-02T06:16:11Zoai:repositorio.unesp.br:11449/170441Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-02T06:16:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
title |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
spellingShingle |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes Lanaro, Carolina |
title_short |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
title_full |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
title_fullStr |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
title_full_unstemmed |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
title_sort |
A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes |
author |
Lanaro, Carolina |
author_facet |
Lanaro, Carolina Franco-Penteado, Carla F. Silva, Fabio H. Fertrin, Kleber Y. dos Santos, Jean Leandro Wade, Marlene Yerigenahally, Shobha de Melo, Thais R. Chin, Chung Man Kutlar, Abdullah Meiler, Steffen E. Costa, Fernando Ferreira |
author_role |
author |
author2 |
Franco-Penteado, Carla F. Silva, Fabio H. Fertrin, Kleber Y. dos Santos, Jean Leandro Wade, Marlene Yerigenahally, Shobha de Melo, Thais R. Chin, Chung Man Kutlar, Abdullah Meiler, Steffen E. Costa, Fernando Ferreira |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Lanaro, Carolina Franco-Penteado, Carla F. Silva, Fabio H. Fertrin, Kleber Y. dos Santos, Jean Leandro Wade, Marlene Yerigenahally, Shobha de Melo, Thais R. Chin, Chung Man Kutlar, Abdullah Meiler, Steffen E. Costa, Fernando Ferreira |
description |
Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 2018-12-11T16:50:49Z 2018-12-11T16:50:49Z |
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.exphem.2017.10.003 Experimental Hematology. 1873-2399 0301-472X http://hdl.handle.net/11449/170441 10.1016/j.exphem.2017.10.003 2-s2.0-85036647241 2-s2.0-85036647241.pdf 9734333607975413 0000-0003-4141-0455 |
url |
http://dx.doi.org/10.1016/j.exphem.2017.10.003 http://hdl.handle.net/11449/170441 |
identifier_str_mv |
Experimental Hematology. 1873-2399 0301-472X 10.1016/j.exphem.2017.10.003 2-s2.0-85036647241 2-s2.0-85036647241.pdf 9734333607975413 0000-0003-4141-0455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Experimental Hematology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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 |
|
_version_ |
1803046764793561088 |