Inflammation

pp 1–15 | Cite as

A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti-inflammatory Drugs

  • Marcus Vinicius P. S. Nascimento
  • Antonio C. M. Munhoz
  • Lais C. Theindl
  • Eduarda Talita B. Mohr
  • Najla Saleh
  • Eduardo B. Parisotto
  • Thaís A. Rossa
  • Ariane Zamoner
  • Tania B. Creczynski-Pasa
  • Fabíola B. Filippin-Monteiro
  • Marcus M. Sá
  • Eduardo Monguilhott Dalmarco
ORIGINAL ARTICLE
  • 33 Downloads

Abstract

Although inflammation is a biological phenomenon that exists to protect the host against infections and/or related problems, its unceasing activation results in the aggravation of several medical conditions. Imidazoles, whether natural or synthetic, are molecules related to a broad spectrum of biological effects, including anti-inflammatory properties. In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for their in vitro anti-inflammatory activity. The effect of the selected molecules was confirmed in an in vivo inflammatory model. We also analyzed whether the effects were caused by inhibition of nuclear factor kappa B (NF-κB) transcription factor transmigration. Of the eight imidazoles tested, methyl 1-allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric oxide metabolites and pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β) secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte migration and exudate formation in the pleural cavity of mice challenged with carrageenan. Furthermore, imidazole 8 reverted the oxidative stress pattern triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase, superoxide dismutase, catalase, and glutathione S-transferase activities and reducing the production of nitric oxide metabolites and thiobarbituric acid-reactive substances. Finally, these effects can be attributed, at least in part, to the ability of this compound to prevent NF-κB transmigration. In this context, our results demonstrate that imidazole 8 has promising potential as a prototype for the development of a new anti-inflammatory drug to treat inflammatory conditions in which NF-κB and oxidative stress play a prominent role.

Graphical Abstract

KEY WORDS

Inflammation imidazole J774 pleurisy oxidative stress NF-κB 

Notes

Acknowledgments

The authors are grateful to Fiona Robson for her assistance in proofreading and correcting the English language of this text.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures in studies involving animals were performed in accordance with the ethical standards of the institution (CEUA/UFSC Protocol PP00965).

Supplementary material

10753_2018_782_MOESM1_ESM.pdf (406 kb)
ESM 1 Supplementary materials on the general procedure for the synthesis of imidazoles 1–8, including 1H and 13C NMR spectra. (PDF 406 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Marcus Vinicius P. S. Nascimento
    • 1
  • Antonio C. M. Munhoz
    • 1
  • Lais C. Theindl
    • 2
  • Eduarda Talita B. Mohr
    • 1
  • Najla Saleh
    • 1
  • Eduardo B. Parisotto
    • 3
  • Thaís A. Rossa
    • 4
  • Ariane Zamoner
    • 3
  • Tania B. Creczynski-Pasa
    • 5
  • Fabíola B. Filippin-Monteiro
    • 2
  • Marcus M. Sá
    • 4
  • Eduardo Monguilhott Dalmarco
    • 2
  1. 1.Postgraduation Program in PharmacyFederal University of Santa CatarinaFlorianopolisBrazil
  2. 2.Department of Clinical Analysis, Centre of Health SciencesFederal University of Santa CatarinaFlorianópolisBrazil
  3. 3.Department of BiochemistryFederal University of Santa CatarinaFlorianopolisBrazil
  4. 4.Department of ChemistryFederal University of Santa CatarinaFlorianopolisBrazil
  5. 5.Department of Pharmaceutical SciencesFederal University of Santa CatarinaFlorianopolisBrazil

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