Title:Synthesis and In vitro and In silico Anti-inflammatory Activity of New
Thiazolidinedione-quinoline Derivatives
Volume: 24
Issue: 14
Author(s): Sandra Elizabeth Barbosa da Silva*, José Arion da Silva Moura, Jeann Fabiann Branco Júnior, Paulo André Teixeira de Moraes Gomes, Simão Kalebe Silva de Paula, Douglas Carvalho Francisco Viana, Eduardo Augusto Vasconcelos de Freitas Ramalho, João Victor de Melo Gomes, Michelly Cristiny Pereira, Maira Galdino da Rocha Pitta, Ivan da Rocha Pitta and Marina Galdino da Rocha Pitta
Affiliation:
- Federal University of Pernambuco, Laboratory of Design and Drug Synthesis - LPSF, Recife, PE, Brazil
- Federal University of Pernambuco, Keizo Asami Institute - iLIKA, Recife, PE, Brazil
Keywords:
Inflammation, Cyclooxygenase 2, PPARγ, IFN-γ, TNF-α, Thiazoidinedione, Quinoline.
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.
