Synthesis and pharmacological evaluation of pomalidomide derivatives useful for sickle cell disease treatment

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorZucker School of Medicine at Hofstra/Northwell-
Autor(es): dc.contributorThe Feinstein Institutes for Medical Research-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.creatorde Melo, Thais Regina Ferreira [UNESP]-
Autor(es): dc.creatorDulmovits, Brian-
Autor(es): dc.creatorFernandes, Guilherme Felipe dos Santos [UNESP]-
Autor(es): dc.creatorde Souza, Cristiane M.-
Autor(es): dc.creatorLanaro, Carolina-
Autor(es): dc.creatorHe, Minghzu-
Autor(es): dc.creatorAl Abed, Yousef-
Autor(es): dc.creatorChung, Man Chin [UNESP]-
Autor(es): dc.creatorBlanc, Lionel-
Autor(es): dc.creatorCosta, Fernando Ferreira-
Autor(es): dc.creatordos Santos, Jean Leandro [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:47:11Z-
Data de disponibilização: dc.date.available2022-02-22T00:47:11Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-09-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.bioorg.2021.105077-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/206475-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/206475-
Descrição: dc.descriptionFetal hemoglobin (HbF) induction constitutes a valuable and validated approach to treat the symptoms of sickle cell disease (SCD). Here, we synthesized pomalidomide–nitric oxide (NO) donor derivatives (3a–f) and evaluated their suitability as novel HbF inducers. All compounds demonstrated different capacities of releasing NO, ranging 0.3–30.3%. Compound 3d was the most effective HbF inducer for CD34+ cells, exhibiting an effect similar to that of hydroxyurea. We investigated the mode of action of compound 3d for HbF induction by studying the in vitro alterations in the levels of transcription factors (BCL11A, IKAROS, and LRF), inhibition of histone deacetylase enzymes (HDAC-1 and HDAC-2), and measurement of cGMP levels. Additionally, compound 3d exhibited a potent anti-inflammatory effect similar to that of pomalidomide by reducing the TNF-α levels in human mononuclear cells treated with lipopolysaccharides up to 58.6%. Chemical hydrolysis studies revealed that compound 3d was stable at pH 7.4 up to 24 h. These results suggest that compound 3d is a novel HbF inducer prototype with the potential to treat SCD symptoms.-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Pharmaceutical Sciences-
Descrição: dc.descriptionDepartment of Molecular Medicine and Pediatrics Zucker School of Medicine at Hofstra/Northwell-
Descrição: dc.descriptionLaboratory of Developmental Erythropoiesis Les Nelkin Memorial Pediatric Oncology Laboratory The Feinstein Institutes for Medical Research-
Descrição: dc.descriptionFaculty of Medical Sciences State University of Campinas - UNICAMP-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Pharmaceutical Sciences-
Idioma: dc.languageen-
Relação: dc.relationBioorganic Chemistry-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectEpigenetics-
Palavras-chave: dc.subjectFetal hemoglobin inducers-
Palavras-chave: dc.subjectNitric oxide-
Palavras-chave: dc.subjectNO-donors-
Palavras-chave: dc.subjectPomalidomide-
Palavras-chave: dc.subjectSickle Cell Disease-
Título: dc.titleSynthesis and pharmacological evaluation of pomalidomide derivatives useful for sickle cell disease treatment-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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