New Oxazolidines Inhibit the Secretion of IFN-γ and IL-17 by PBMCS from Moderate to Severe Asthmatic Patients

Med Chem. 2021;17(3):289-297. doi: 10.2174/1573406416666200910151950.

Abstract

Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies.

Objective: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma.

Methods: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed.

Results: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma.

Conclusion: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.

Keywords: Airway hyperresponsiveness; allergy; anti-inflammatory; cytokine; oxazolidine; treatment resistance.

MeSH terms

  • Asthma / drug therapy
  • Asthma / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Interferon-gamma / metabolism*
  • Interleukin-17 / metabolism*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism*
  • Molecular Docking Simulation
  • Oxazoles / chemistry*
  • Oxazoles / metabolism
  • Oxazoles / pharmacology*
  • Oxazoles / therapeutic use
  • Protein Conformation
  • Receptors, Neurokinin-1 / chemistry
  • Receptors, Neurokinin-1 / metabolism

Substances

  • Interleukin-17
  • Oxazoles
  • Receptors, Neurokinin-1
  • oxazolidine
  • Interferon-gamma