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Curr Top Med Chem ; 24(14): 1264-1277, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38523516

RESUMEN

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.


Asunto(s)
Simulación del Acoplamiento Molecular , Quinolinas , Tiazolidinedionas , Quinolinas/farmacología , Quinolinas/química , Quinolinas/síntesis química , Tiazolidinedionas/farmacología , Tiazolidinedionas/síntesis química , Tiazolidinedionas/química , Estructura Molecular , Humanos , Supervivencia Celular/efectos de los fármacos , Relación Estructura-Actividad , Animales , PPAR gamma/agonistas , PPAR gamma/metabolismo , Relación Dosis-Respuesta a Droga , Ratones , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Ciclooxigenasa 2/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Factor de Necrosis Tumoral alfa/metabolismo
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