Synthesis and In vitro and In silico Anti-inflammatory Activity of New
Thiazolidinedione-quinoline Derivatives

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; Marina   Galdino   da Rocha Pitta

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.

Graphical Abstract

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Cite As

Current Topics in Medicinal Chemistry

Synthesis and In vitro and In silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives

Abstract

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