Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

Detalhes bibliográficos
Autor(a) principal: dos Santos, Jean Leandro [UNESP]
Data de Publicação: 2012
Outros Autores: Moreira, Vanessa, Campos, Michel Leandro [UNESP], Chelucci, Rafael Consolin [UNESP], Barbieri, Karina Pereira [UNESP], Maggio de Castro Souto, Pollyana Cristina, Matsubara, Marcio Hideki, Teixeira, Catarina, Bosquesi, Priscila Longhin [UNESP], Peccinini, Rosangela Goncalves [UNESP], Chin, Chung Man [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/ijms131115305
http://hdl.handle.net/11449/7922
Resumo: Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.
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spelling Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration EffectNSAIDsanti-inflammatorydiclofenacprodrugsmolecular modificationlactamCOX-inhibitorbioconversionchronic inflammationLong-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)PADC-UNESPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Instituto Nacional de Ciência e Tecnologia-Inovacao Farmaceutica (INCT-if)Sch Pharmaceut Sci UNESP, Drugs & Med Dept, Lapdesf Lab Res & Drug Dev, BR-14801902 Araraquara, SP, BrazilInstituto Butantan, Inflammat Unit, Pharmacol Lab, BR-05503900 São Paulo, BrazilSch Pharmaceut Sci UNESP, Nat Act Principles & Toxicol Dept, BR-14801902 Araraquara, SP, BrazilSch Pharmaceut Sci UNESP, Drugs & Med Dept, Lapdesf Lab Res & Drug Dev, BR-14801902 Araraquara, SP, BrazilSch Pharmaceut Sci UNESP, Nat Act Principles & Toxicol Dept, BR-14801902 Araraquara, SP, BrazilFAPESP: 09/12664-5FAPESP: 10/12495-6PADC-UNESP: 107/10Mdpi AgUniversidade Estadual Paulista (Unesp)Instituto Butantandos Santos, Jean Leandro [UNESP]Moreira, VanessaCampos, Michel Leandro [UNESP]Chelucci, Rafael Consolin [UNESP]Barbieri, Karina Pereira [UNESP]Maggio de Castro Souto, Pollyana CristinaMatsubara, Marcio HidekiTeixeira, CatarinaBosquesi, Priscila Longhin [UNESP]Peccinini, Rosangela Goncalves [UNESP]Chin, Chung Man [UNESP]2014-05-20T13:25:02Z2014-05-20T13:25:02Z2012-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15305-15320application/pdfhttp://dx.doi.org/10.3390/ijms131115305International Journal of Molecular Sciences. Basel: Mdpi Ag, v. 13, n. 11, p. 15305-15320, 2012.1422-0067http://hdl.handle.net/11449/792210.3390/ijms131115305WOS:000311425000095WOS000311425000095.pdf106674342392909397343336079754130000-0003-4141-0455Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciences3.6871,260info:eu-repo/semantics/openAccess2024-06-24T14:51:51Zoai:repositorio.unesp.br:11449/7922Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:01:21.271938Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
title Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
spellingShingle Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
dos Santos, Jean Leandro [UNESP]
NSAIDs
anti-inflammatory
diclofenac
prodrugs
molecular modification
lactam
COX-inhibitor
bioconversion
chronic inflammation
title_short Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
title_full Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
title_fullStr Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
title_full_unstemmed Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
title_sort Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
author dos Santos, Jean Leandro [UNESP]
author_facet dos Santos, Jean Leandro [UNESP]
Moreira, Vanessa
Campos, Michel Leandro [UNESP]
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Maggio de Castro Souto, Pollyana Cristina
Matsubara, Marcio Hideki
Teixeira, Catarina
Bosquesi, Priscila Longhin [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
Chin, Chung Man [UNESP]
author_role author
author2 Moreira, Vanessa
Campos, Michel Leandro [UNESP]
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Maggio de Castro Souto, Pollyana Cristina
Matsubara, Marcio Hideki
Teixeira, Catarina
Bosquesi, Priscila Longhin [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
Chin, Chung Man [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Instituto Butantan
dc.contributor.author.fl_str_mv dos Santos, Jean Leandro [UNESP]
Moreira, Vanessa
Campos, Michel Leandro [UNESP]
Chelucci, Rafael Consolin [UNESP]
Barbieri, Karina Pereira [UNESP]
Maggio de Castro Souto, Pollyana Cristina
Matsubara, Marcio Hideki
Teixeira, Catarina
Bosquesi, Priscila Longhin [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
Chin, Chung Man [UNESP]
dc.subject.por.fl_str_mv NSAIDs
anti-inflammatory
diclofenac
prodrugs
molecular modification
lactam
COX-inhibitor
bioconversion
chronic inflammation
topic NSAIDs
anti-inflammatory
diclofenac
prodrugs
molecular modification
lactam
COX-inhibitor
bioconversion
chronic inflammation
description Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.
publishDate 2012
dc.date.none.fl_str_mv 2012-11-01
2014-05-20T13:25:02Z
2014-05-20T13:25:02Z
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/ijms131115305
International Journal of Molecular Sciences. Basel: Mdpi Ag, v. 13, n. 11, p. 15305-15320, 2012.
1422-0067
http://hdl.handle.net/11449/7922
10.3390/ijms131115305
WOS:000311425000095
WOS000311425000095.pdf
1066743423929093
9734333607975413
0000-0003-4141-0455
url http://dx.doi.org/10.3390/ijms131115305
http://hdl.handle.net/11449/7922
identifier_str_mv International Journal of Molecular Sciences. Basel: Mdpi Ag, v. 13, n. 11, p. 15305-15320, 2012.
1422-0067
10.3390/ijms131115305
WOS:000311425000095
WOS000311425000095.pdf
1066743423929093
9734333607975413
0000-0003-4141-0455
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Molecular Sciences
3.687
1,260
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15305-15320
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
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