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Synthesis and In vitro and In silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.
da Silva, Sandra Elizabeth Barbosa; da Silva Moura, José Arion; Branco Júnior, Jeann Fabiann; de Moraes Gomes, Paulo André Teixeira; de Paula, Simão Kalebe Silva; Viana, Douglas Carvalho Francisco; de Freitas Ramalho, Eduardo Augusto Vasconcelos; de Melo Gomes, João Victor; Pereira, Michelly Cristiny; da Rocha Pitta, Maira Galdino; da Rocha Pitta, Ivan; da Rocha Pitta, Marina Galdino.
Afiliação
  • da Silva SEB; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • da Silva Moura JA; Federal University of Pernambuco, Keizo Asami Institute - iLIKA, Recife, PE, Brazil.
  • Branco Júnior JF; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • de Moraes Gomes PAT; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • de Paula SKS; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • Viana DCF; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • de Freitas Ramalho EAV; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • de Melo Gomes JV; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • Pereira MC; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • da Rocha Pitta MG; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
  • da Rocha Pitta I; Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches - LINAT, Recife, PE, Brazil.
  • da Rocha Pitta MG; Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil.
Curr Top Med Chem ; 24(14): 1264-1277, 2024.
Article em En | MEDLINE | ID: mdl-38523516
ABSTRACT

BACKGROUND:

Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity.

OBJECTIVES:

Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade.

METHODS:

After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets.

RESULTS:

LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol.

CONCLUSION:

These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolinas / Tiazolidinedionas / Simulação de Acoplamento Molecular Limite: Animals / Humans Idioma: En Revista: Curr Top Med Chem Assunto da revista: QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Emirados Árabes Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolinas / Tiazolidinedionas / Simulação de Acoplamento Molecular Limite: Animals / Humans Idioma: En Revista: Curr Top Med Chem Assunto da revista: QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Emirados Árabes Unidos