Hidalgo ‐ Figueroa, Sergio, Ramírez ‐ Espinosa, Juan J., Estrada ‐ Soto, Samuel, Almanza ‐ Pérez, Julio C., Román ‐ Ramos, Rubén, Alarcón ‐ Aguilar, Francisco J., Hernández ‐ Rosado, Jesús V., Moreno ‐ Díaz, Hermenegilda, Díaz ‐ Coutiño, Daniel, and Navarrete ‐ Vázquez, Gabriel
A small series of thiazolidine-2,4-dione and barbituric acid derivatives 1-4 was prepared using a short synthetic route, and all compounds were characterized by elemental analysis, mass spectrometry, and NMR (1 H, 13 C) spectroscopy. Their in vitro relative expression of peroxisome proliferator-activated receptor &agr1; and peroxisome proliferator-activated receptor &ggr1; was evaluated. Compound 1 showed an increase in the m RNA expression of both peroxisome proliferator-activated receptor isoforms, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/kg single dose using a non-insulin-dependent diabetes mellitus rat model. The results indicated a significant decrease in plasma glucose levels. Additionally, we performed a molecular docking of compound 1 into the ligand binding pocket of peroxisome proliferator-activated receptor &agr1; and peroxisome proliferator-activated receptor &ggr1;. In these binding models, compound 1 may bind into the active site of both isoforms showing important short contacts with the peroxisome proliferator-activated receptor &ggr1; residues: Tyr 473, His 449, Ser 289, His 323; and peroxisome proliferator-activated receptor α residues: Tyr 464, His 440, Ser 280 and Tyr 314. [ABSTRACT FROM AUTHOR]