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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.)

Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)coumarin derivatives: Effect on inducible nitric oxide synthase

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Author(s):
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Stefani, Helio A. [1] ; Gueogjan, Karina [1] ; Manarin, Flavia [1] ; Farsky, Sandra H. P. [2] ; Zukerman-Schpector, Julio [3] ; Caracelli, Ignez [4] ; Pizano Rodrigues, Sergio R. [5] ; Muscara, Marcelo N. [6] ; Teixeira, Simone A. [6] ; Santin, Jose R. [2] ; Machado, Isabel D. [2] ; Bolonheis, Simone M. [2] ; Curi, Rui [7] ; Vinolo, Marco A. [7]
Total Authors: 14
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Farm, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil
[3] Univ Fed Sao Carlos, Dept Quim, BR-13560 Sao Carlos, SP - Brazil
[4] Univ Fed Sao Carlos, Dept Fis, BioMat, BR-13560 Sao Carlos, SP - Brazil
[5] Univ Fed Sao Carlos, Programa Posgrad Biotecnol, BR-13560 Sao Carlos, SP - Brazil
[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 Sao Paulo - Brazil
[7] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 7
Document type: Journal article
Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 58, p. 117-127, DEC 2012.
Web of Science Citations: 39
Abstract

A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-alpha secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that it pi center dot center dot center dot pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored. (C) 2012 Elsevier Masson SAS. All rights reserved. (AU)

FAPESP's process: 10/15677-8 - Synthesis of alpha-substituted styrenes
Grantee:Flávia Giovana Manarin
Support Opportunities: Scholarships in Brazil - Post-Doctoral