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.
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 wide range of diseases, including rheumatoid arthritis, sepsis and inflammatory bowel disease. In the literature, 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 a pharmacological activity.
Objective:
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.