Synthesis, in vitro and in silico studies of a PPARγ and GLUT-4 modulator with hypoglycemic effect.

Navarrete-Vázquez G, Torres-Gómez H, Hidalgo-Figueroa S, Ramírez-Espinosa JJ, Estrada-Soto S, Medina-Franco JL, León-Rivera I, Alarcón-Aguilar FJ, Almanza-Pérez JC (2014) Synthesis, in vitro and in silico studies of a PPARγ and GLUT-4 modulator with hypoglycemic effect. Bioorg Med Chem Lett 24(18), 4575-4579.

Abstract

Compound {4-[({4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}acetyl)amino]phenoxy}acetic acid (1) was prepared and the in vitro relative expression of PPARγ, GLUT-4 and PPARα, was estimated. Compound 1 showed an increase of 2-fold in the mRNA expression of PPARγ isoform, 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 (NIDDM) rat model. The in vivo results indicated a significant decrease of plasma glucose levels, during the 7 h post-administration. Also, we performed a molecular docking of compound 1 into the ligand binding pocket of PPARγ, showing important short contacts with residues Ser289, His323 and His449 in the active site.

Leibniz-HKI-Autor*innen

Héctor Torres-Gomez

Identifier

doi: S0960-894X(14)00792-6

PMID: 25131539