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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Chemical synthesis, docking studies and biological effects of a pan peroxisome proliferator-activated receptor agonist and cyclooxygenase inhibitor

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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