| Full text | |
| Author(s): Show less - |
Santin, Jose Roberto
[1]
;
Uchoa, Flavia D. T.
[2]
;
Lima, Maria do Carmo A.
[2]
;
Rabello, Marcelo M.
[3]
;
Machado, Isabel Daufenback
[1]
;
Hernandes, Marcelo Z.
[3]
;
Amato, Angelica A.
[4]
;
Milton, Flora Aparecida
[5, 4]
;
Webb, Paul
[5]
;
Rocha Neves, Francisco de Assis
[4]
;
Galdino, Suely L.
[2]
;
Pitta, Ivan Rocha
[2]
;
Farsky, Sandra H. P.
[1]
Total Authors: 13
|
| Affiliation: | [1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, BR-05508900 Sao Paulo - Brazil
[2] Univ Fed Pernambuco, LPSF, Recife, PE - Brazil
[3] Univ Fed Pernambuco, LQTM, Dept Ciencias Farmaceut, Recife, PE - Brazil
[4] Univ Brasilia, Fac Ciencias Saude, Dept Ciencias Farmaceut, Lab Farmacol Mol, BR-70910900 Brasilia, DF - Brazil
[5] Methodist Hosp, Res Inst, Diabet Res Ctr, Houston, TX 77030 - USA
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | European Journal of Pharmaceutical Sciences; v. 48, n. 4-5, p. 689-697, MAR 12 2013. |
| Web of Science Citations: | 13 |
| Abstract | |
The compound (5Z)-5-{[}(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolid ine-2,4-dione (LYSO-7) was synthesised in order to obtain a new type of anti-inflammatory drug, designed with hybrid features to inhibit cyclooxygenase (COX) and also to activate peroxisome proliferator-activated receptor (PPAR). Results obtained from docking (in silico) studies corroborated with experimental data, showing the potential affinity between the studied ligand and targets. The specificity of LYSO-7 for COX-enzymes was detected by the inhibition of COX-1 and COX-2 activities by 30% and 20%, respectively. In transactivation reporter gene assays LYSO-07 showed a pan partial agonist effect on the three PPAR subtypes (PPAR gamma, PPAR alpha and PPAR beta/delta). The agonist action on PPAR gamma was also observed by a pharmacological approach, as the reduction in the Escherichia coli lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) secretion and nitric oxide (NO) production by mouse neutrophils was blocked by GW9962, a specific PPAR gamma antagonist. Additionally, the in vivo effect was measured by reduced carrageenan-induced neutrophil influx into the subcutaneous tissue of mice. Taken together, these data show that LYSO-7 displays a potent in vivo anti-inflammatory effect during the innate acute response, which is dependent on its associated COX inhibitory activities and PPAR activation. (C) 2013 Elsevier B.V. All rights reserved. (AU) | |
| FAPESP's process: | 10/17175-0 - Effect of PPAR agonist LYSO-07 on installation and healing of gastric ulcers in mice |
| Grantee: | José Roberto Santin |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 11/01848-8 - Evaluation of gastroprotective activity of PPAR agonist Lyso-07 and chlorogenic acid |
| Grantee: | Sandra Helena Poliselli Farsky |
| Support Opportunities: | Regular Research Grants |