Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , , |
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. |
id |
UNSP_384988298751411ece98cc04565abe90 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/7922 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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 |
|
_version_ |
1808129012537491456 |