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

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.