Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/molecules16042982 http://hdl.handle.net/11449/7498 |
Resumo: | The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl] ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1-C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms. |
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Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Diseasegenotoxicity assaymicronucleussickle cellphthalimide derivativesThe compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl] ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1-C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms.Fundação para o Desenvolvimento da UNESP (FUNDUNESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Programa de Apoio ao Desenvolvimento Científico da Faculdade de Ciências Farmacêuticas da UNESP (PADC)Univ Estadual Paulista UNESP, Lab Pesquisa & Desenvolvimento Farmacos Lapdesf, Dept Farmacos & Med, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, BrazilUniv Estadual Paulista UNESP, Dept Ciencias Biol, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, BrazilUniv Fed Rio de Janeiro, Lab Avaliacao & Sintese Subst Bioat LASSBio, Fac Farm, Ctr Ciencias Saude,Ilha Fundao, BR-21944190 Rio de Janeiro, BrazilUniv Estadual Paulista UNESP, Lab Pesquisa & Desenvolvimento Farmacos Lapdesf, Dept Farmacos & Med, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, BrazilUniv Estadual Paulista UNESP, Dept Ciencias Biol, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, BrazilFAPESP: 10/12495-6PADC-FCFar UNESP: 107/10Mdpi AgUniversidade Estadual Paulista (Unesp)Universidade Federal do Rio de Janeiro (UFRJ)dos Santos, Jean Leandro [UNESP]Bosquesi, Priscila Longhin [UNESP]Varanda, Eliana Aparecida [UNESP]Lima, Lidia Moreira [UNESP]Chin, Chung Man [UNESP]2014-05-20T13:24:18Z2014-05-20T13:24:18Z2011-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2982-2989application/pdfhttp://dx.doi.org/10.3390/molecules16042982Molecules. Basel: Mdpi Ag, v. 16, n. 4, p. 2982-2989, 2011.1420-3049http://hdl.handle.net/11449/749810.3390/molecules16042982WOS:000289236200018WOS000289236200018.pdf750193023649667097343336079754130000-0003-4141-0455Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecules3.0980,855info:eu-repo/semantics/openAccess2024-06-24T13:45:50Zoai:repositorio.unesp.br:11449/7498Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:39:31.800107Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
title |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
spellingShingle |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease dos Santos, Jean Leandro [UNESP] genotoxicity assay micronucleus sickle cell phthalimide derivatives |
title_short |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
title_full |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
title_fullStr |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
title_full_unstemmed |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
title_sort |
Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease |
author |
dos Santos, Jean Leandro [UNESP] |
author_facet |
dos Santos, Jean Leandro [UNESP] Bosquesi, Priscila Longhin [UNESP] Varanda, Eliana Aparecida [UNESP] Lima, Lidia Moreira [UNESP] Chin, Chung Man [UNESP] |
author_role |
author |
author2 |
Bosquesi, Priscila Longhin [UNESP] Varanda, Eliana Aparecida [UNESP] Lima, Lidia Moreira [UNESP] Chin, Chung Man [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal do Rio de Janeiro (UFRJ) |
dc.contributor.author.fl_str_mv |
dos Santos, Jean Leandro [UNESP] Bosquesi, Priscila Longhin [UNESP] Varanda, Eliana Aparecida [UNESP] Lima, Lidia Moreira [UNESP] Chin, Chung Man [UNESP] |
dc.subject.por.fl_str_mv |
genotoxicity assay micronucleus sickle cell phthalimide derivatives |
topic |
genotoxicity assay micronucleus sickle cell phthalimide derivatives |
description |
The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl] ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1-C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-04-01 2014-05-20T13:24:18Z 2014-05-20T13:24:18Z |
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/molecules16042982 Molecules. Basel: Mdpi Ag, v. 16, n. 4, p. 2982-2989, 2011. 1420-3049 http://hdl.handle.net/11449/7498 10.3390/molecules16042982 WOS:000289236200018 WOS000289236200018.pdf 7501930236496670 9734333607975413 0000-0003-4141-0455 |
url |
http://dx.doi.org/10.3390/molecules16042982 http://hdl.handle.net/11449/7498 |
identifier_str_mv |
Molecules. Basel: Mdpi Ag, v. 16, n. 4, p. 2982-2989, 2011. 1420-3049 10.3390/molecules16042982 WOS:000289236200018 WOS000289236200018.pdf 7501930236496670 9734333607975413 0000-0003-4141-0455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecules 3.098 0,855 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
2982-2989 application/pdf |
dc.publisher.none.fl_str_mv |
Mdpi Ag |
publisher.none.fl_str_mv |
Mdpi Ag |
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 |
|
_version_ |
1808128962653585408 |