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

被引:0
|
作者
Cavalcanti Santos, Renata Virginia [1 ]
Constantino Cunha, Eudes Gustavo [1 ]
Vieira de Mello, Gabriela Souto [1 ]
Rizzo, Jose Angelo [2 ]
de Oliveira, Jamerson Ferreira [3 ]
Alves de Lima, Maria do Carmo [3 ]
Pitta, Ivan da Rocha [1 ]
da Rocha Pitta, Maira Galdino [1 ]
Barreto de Melo Rego, Moacyr Jesus [1 ]
机构
[1] Univ Fed Pernambuco, Lab Imunomodulacao & Novas Abordagens Terapeut LI, Nucleo Pesquisa Inovacao Terapeut Suely Galdino N, Recife, PE, Brazil
[2] Univ Fed Pernambuco, Hosp Clin, Serv Pneumol, Recife, PE, Brazil
[3] Univ Fed Pernambuco, Dept Antibiot, Lab Quim & Inovacao Terapeut LQIT, Recife, PE, Brazil
关键词
Airway hyperresponsiveness; allergy; oxazolidine; anti-inflammatory; cytokine; treatment resistance; ALLERGIC AIRWAY INFLAMMATION; RECEPTOR ANTAGONISM FAILS; TACHYKININ NK1 RECEPTOR; EXPERIMENTAL-MODEL; MOUSE MODEL; NEUROKININ-1; HYPERRESPONSIVENESS; CELLS; BRODALUMAB; EOSINOPHILIA;
D O I
10.2174/1573406416666200910151950
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:289 / 297
页数:9
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