A short series of antidiabetic sulfonylureas exhibit multiple ligand PPARgamma-binding patterns.
The present work explores the PPARgamma-activating properties of a series of eight sulfonylureas, using transfection experiments with 293T cells, and rosiglitazone as a reference PPARgamma agonist. In the same time, results from these in vitro experiments are compared to those generated by a sound in silico PPARgamma-ligand docking procedure combined to a simple and astute strategy analysis. The latter consists of building up a dendrogram (decision tree-like diagram) by applying three successive criteria, namely stability, conformational shape and H-binding strength of the docked sulfonylurea or rosiglitazone. This original dendrogram approach avers to be a successful way to account for our biochemical data. It discriminates also various PPARgamma-binding patterns from our small series of compounds. The recognition of these patterns is extremely important because of the extraordinary potentialities of PPARgamma ligands as therapeutic agents in diabetes, cancer, cardiovascular and neurological disorders.
Arrault
Alban
A
Chemoinformatics Group, Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d'Orléans, BP 6759,.Orléans Cedex 2, France.
Rocchi
Stéphane
S
Picard
Frédéric
F
Maurois
Pierre
P
Pirotte
Bernard
B
Vamecq
Joseph
J
D000465:Algorithms; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists*; D011485:Protein Binding; D012984:Software; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D013453:Sulfonylurea Compounds