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Please use this identifier to cite or link to this item: http://acervodigital.unesp.br/handle/11449/26193
Title: 
Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline
Author(s): 
Institution: 
  • Universidade Federal do Rio de Janeiro (UFRJ)
  • Universidade Federal de Alfenas (UNIFAL)
  • Universidade Federal de Alagoas (UFAL)
  • Universidade Estadual Paulista (UNESP)
ISSN: 
  • 0009-2363
  • 1347-5223
Abstract: 
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.
Issue Date: 
1-Apr-2008
Citation: 
Chemical & Pharmaceutical Bulletin. Tokyo: Pharmaceutical Soc Japan, v. 56, n. 4, p. 407-412, 2008.
Time Duration: 
407-412
Publisher: 
Pharmaceutical Soc Japan
Keywords: 
  • cassia spectabilis
  • piperidine alkaloid
  • (-)-3-O-acetyl-spectaline
  • antinociceptive
  • anti-inflammatory
Source: 
http://dx.doi.org/10.1248/cpb.56.407
URI: 
Access Rights: 
Acesso aberto
Type: 
outro
Source:
http://repositorio.unesp.br/handle/11449/26193
Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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