Laboratorio de Imunomodulacao e Novas Abordagens Terapeuticas (LINAT), Nucleo de Pesquisa em Inovacao Terapeutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Brazil.
Servico de Pneumologia, Hospital das Clinicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
Med Chem. 2021;17(3):289-297. doi: 10.2174/1573406416666200910151950.
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.
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.
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.
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.
The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.
中度至重度哮喘可由多种促炎细胞因子诱导，如 IL-17 和 IFN-γ，这些细胞因子也与治疗抵抗和气道高反应性有关。唑烷酮类化合物作为一种治疗哮喘的新方法出现，因为之前的研究提出了一些化学特性。
本研究旨在评估两种新型唑烷酮衍生物（LPSF/NB-12 和 -13）对中重度哮喘患者单核细胞中 IL-17A 和 IFN-γ 的调节作用。
首先使用 SWISS-ADME 研究唑烷酮衍生物的潜在靶标。在合成化合物后，分析细胞毒性和细胞因子水平。
我们证明 LPSF/NB-12 和 -13 以集中的方式减少了来自哮喘患者外周血单核细胞中 IFN-γ 和 IL-17 的产生。我们的计算机分析显示，速激肽-1 受体是这两种化合物的共同靶标，它负责中度和重度哮喘的多种促炎作用。
这项工作展示了一种针对哮喘的新方法，值得进一步研究其作用机制。
