Journal
MEDICINAL CHEMISTRY
Volume 17, Issue 3, Pages 289-297Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1573406416666200910151950
Keywords
Airway hyperresponsiveness; allergy; oxazolidine; anti-inflammatory; cytokine; treatment resistance
Categories
Funding
- Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)
- Instituto de Ciencia e Tecnologia-Inovacao Farmaceutica (INCT_If)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de pessoal de Nivel Superior (CAPES)
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This study evaluated the IL-17A and IFN-gamma modulatory effect of two new oxazolidine derivatives on mononucleated cells of patients with moderate and severe asthma. The results showed that the compounds reduced IFN-gamma and IL-17 production in a concentrated manner in peripheral blood mononucleated cells from asthmatic patients. In silico analysis revealed the neurokinin-1 receptor as a common target for both compounds, indicating a potential mechanism for their effects.
Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-gamma, 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-gamma 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-gamma 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.
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