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

Author(s):

Renata Virgínia Cavalcanti Santos*, Eudes Gustavo Constantino Cunha, Gabriela Souto Vieira de Mello, José Ângelo Rizzo, Jamerson Ferreira de Oliveira, Maria do Carmo Alves de Lima, Ivan da Rocha Pitta, Maira Galdino da Rocha Pitta and Moacyr Jesus Barreto de Melo Rêgo   Pages 1 - 9 ( 9 )

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.

Method: 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, Oxazolidine, Anti-inflammatory, Cytokine, Treatment resistance

Affiliation:

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Serviço de Pneumologia, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, PE, Laboratório de Química e Inovação Terapêutica (LQIT), Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Laboratório de Química e Inovação Terapêutica (LQIT), Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE



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