Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1248/cpb.56.407 http://hdl.handle.net/11449/26193 |
Resumo: | In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity. |
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Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectalinecassia spectabilispiperidine alkaloid(-)-3-O-acetyl-spectalineantinociceptiveanti-inflammatoryIn early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity.Univ Fed Rio de Janeiro, Fac Farm, Dept Farm, Lab Avaliacao & Sintese Substancias Bioativas, BR-21941902 Rio de Janeiro, BrazilUniv Fed Alfenas, Dept Ciencias Exatas, Lab Fitoquim & Quim Med, BR-37130000 Alfenas, MG, BrazilUniversidade Federal de Alagoas (UFAL), Ctr Ciencias Biol, Dept Fisiol, Lab Farmacol & Imunidade, Maceto, AL USAUniv Estadual Paulista, Inst Quim, BR-14800900 Araraquara, SP, BrazilUniv Estadual Paulista, Inst Quim, BR-14800900 Araraquara, SP, BrazilPharmaceutical Soc JapanUniversidade Federal do Rio de Janeiro (UFRJ)Universidade Federal de Alfenas (UNIFAL)Universidade Federal de Alagoas (UFAL)Universidade Estadual Paulista (Unesp)Viegas, ClaudioAlexandre-Moreira, Magna SuzanaMarissour Fraga, Carlos AlbertoBarreiro, Eliezer JesusBolzani, Vanderlan da Silva [UNESP]Palhares de Miranda, Ana Luisa2014-05-20T14:20:38Z2014-05-20T14:20:38Z2008-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article407-412application/pdfhttp://dx.doi.org/10.1248/cpb.56.407Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 56, n. 4, p. 407-412, 2008.0009-23631347-5223http://hdl.handle.net/11449/2619310.1248/cpb.56.407WOS:0002555067000012-s2.0-42049097211WOS000255506700001.pdf4484083685251673Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengChemical & Pharmaceutical Bulletin1.2580,3640,364info:eu-repo/semantics/openAccess2023-11-23T06:13:31Zoai:repositorio.unesp.br:11449/26193Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-11-23T06:13:31Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
title |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
spellingShingle |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline Viegas, Claudio cassia spectabilis piperidine alkaloid (-)-3-O-acetyl-spectaline antinociceptive anti-inflammatory |
title_short |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
title_full |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
title_fullStr |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
title_full_unstemmed |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
title_sort |
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline |
author |
Viegas, Claudio |
author_facet |
Viegas, Claudio Alexandre-Moreira, Magna Suzana Marissour Fraga, Carlos Alberto Barreiro, Eliezer Jesus Bolzani, Vanderlan da Silva [UNESP] Palhares de Miranda, Ana Luisa |
author_role |
author |
author2 |
Alexandre-Moreira, Magna Suzana Marissour Fraga, Carlos Alberto Barreiro, Eliezer Jesus Bolzani, Vanderlan da Silva [UNESP] Palhares de Miranda, Ana Luisa |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal do Rio de Janeiro (UFRJ) Universidade Federal de Alfenas (UNIFAL) Universidade Federal de Alagoas (UFAL) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Viegas, Claudio Alexandre-Moreira, Magna Suzana Marissour Fraga, Carlos Alberto Barreiro, Eliezer Jesus Bolzani, Vanderlan da Silva [UNESP] Palhares de Miranda, Ana Luisa |
dc.subject.por.fl_str_mv |
cassia spectabilis piperidine alkaloid (-)-3-O-acetyl-spectaline antinociceptive anti-inflammatory |
topic |
cassia spectabilis piperidine alkaloid (-)-3-O-acetyl-spectaline antinociceptive anti-inflammatory |
description |
In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-04-01 2014-05-20T14:20:38Z 2014-05-20T14:20:38Z |
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/10.1248/cpb.56.407 Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 56, n. 4, p. 407-412, 2008. 0009-2363 1347-5223 http://hdl.handle.net/11449/26193 10.1248/cpb.56.407 WOS:000255506700001 2-s2.0-42049097211 WOS000255506700001.pdf 4484083685251673 |
url |
http://dx.doi.org/10.1248/cpb.56.407 http://hdl.handle.net/11449/26193 |
identifier_str_mv |
Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 56, n. 4, p. 407-412, 2008. 0009-2363 1347-5223 10.1248/cpb.56.407 WOS:000255506700001 2-s2.0-42049097211 WOS000255506700001.pdf 4484083685251673 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Chemical & Pharmaceutical Bulletin 1.258 0,364 0,364 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
407-412 application/pdf |
dc.publisher.none.fl_str_mv |
Pharmaceutical Soc Japan |
publisher.none.fl_str_mv |
Pharmaceutical Soc Japan |
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_ |
1797789794022981632 |