Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds to Treat Sickle Cell Disease Symptoms. Part II: Furoxan Derivatives

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dc.contributor.authorDos Santos, Jean Leandro [UNESP]
dc.contributor.authorLanaro, Carolina
dc.contributor.authorChelucci, Rafael Consolin [UNESP]
dc.contributor.authorGambero, Sheley [UNESP]
dc.contributor.authorBosquesi, Priscila Longhin [UNESP]
dc.contributor.authorReis, Juliana Santana [UNESP]
dc.contributor.authorLima, Lidia Moreira
dc.contributor.authorCerecetto, Hugo
dc.contributor.authorGonzalez, Mercedes
dc.contributor.authorCosta, Fernando Ferreira
dc.contributor.authorChin, Chung Man [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniv Republica
dc.date.accessioned2014-05-20T13:24:49Z
dc.date.available2014-05-20T13:24:49Z
dc.date.issued2012-09-13
dc.description.abstractPhthalimide derivatives containing furoxanyl subunits as nitric oxide (NO)-donors (3a-g) were designed, synthesized, and evaluated in vitro and in vivo for their potential uses in the oral treatment of sickle cell disease symptoms. All compounds (3a-g) demonstrated NO-donor properties at different levels. Moreover, compounds 3b and 3c demonstrated analgesic activity. Compound 3b was determined to be a promising drug candidate for the aforementioned uses, and it was further evaluated in K562 culture cells to determine its ability to increase levels of gamma-globin expression. After 96 h at 5 mu M, compound 3b was able to induce gamma-globin expression by nearly three times. Mutagenic studies using micronucleus tests in peripheral blood cells of mice demonstrated that compound 3b reduces the mutagenic profile as compared with hydroxyurea. Compound 3b has emerged as a new leading drug candidate with multiple beneficial effects for the treatment of sickle cell disease symptoms and provides an alternative to hydroxyurea treatment.en
dc.description.affiliationUniv Estadual Paulista UNESP, Lapdesf Lab Pesquisa & Desenvolvimento Farmacos, Dept Farmacos & Medicamentos, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, Brazil
dc.description.affiliationUniv Campinas UNICAMP, Haematol & Haemotherapy Ctr, Hemoctr, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Fac Farm, LASSBio Lab Avaliacao & Sintese Subst Bioat, BR-21944971 Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniv Republica, Fac Ciencias, Fac Quim, Grp Quim Med,Lab Quim Organ, Montevideo 11400, Uruguay
dc.description.affiliationUnespUniv Estadual Paulista UNESP, Lapdesf Lab Pesquisa & Desenvolvimento Farmacos, Dept Farmacos & Medicamentos, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 10/12495-6
dc.description.sponsorshipIdFAPESP: 07/56115-0
dc.format.extent7583-7592
dc.identifierhttp://dx.doi.org/10.1021/jm300602n
dc.identifier.citationJournal of Medicinal Chemistry. Washington: Amer Chemical Soc, v. 55, n. 17, p. 7583-7592, 2012.
dc.identifier.doi10.1021/jm300602n
dc.identifier.issn0022-2623
dc.identifier.lattes9734333607975413
dc.identifier.orcid0000-0003-4141-0455
dc.identifier.urihttp://hdl.handle.net/11449/7798
dc.identifier.wosWOS:000308675800021
dc.language.isoeng
dc.publisherAmer Chemical Soc
dc.relation.ispartofJournal of Medicinal Chemistry
dc.relation.ispartofjcr6.253
dc.relation.ispartofsjr2,567
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titleDesign, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds to Treat Sickle Cell Disease Symptoms. Part II: Furoxan Derivativesen
dc.typeArtigo
dcterms.licensehttp://pubs.acs.org/page/policy/nih/index.html
dcterms.rightsHolderAmer Chemical Soc
unesp.author.lattes9734333607975413[11]
unesp.author.orcid0000-0003-4141-0455[11]
unesp.author.orcid0000-0002-0808-0610[9]
unesp.author.orcid0000-0002-2460-2829[1]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.departmentFármacos e Medicamentos - FCFpt

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Araraquara - FCF - Faculdade de Ciências Farmacêuticas