Shaikha S AlNeyadia
1UAE University Al-Ain, UAE
Title: Novel pyrimidine derivatives of rhodanine as pparγ agonists: Design, synthesis, molecular docking and glucose uptake
Biography
Biography: Shaikha S AlNeyadia
Abstract
Rhodanines has become a very interesting class of heterocyclic compounds since the introduction of various glitazones and epalrestat into clinical use for the treatment of type II diabetes mellitus and diabetic complications, respectively. Chemical modifications of these hetero-cycles constantly result in compounds with a wide spectrum of pharmacological activities. In this study, a novel series of pyrimidine derivatives of rhodanine were designed, synthesized, docked against the PPARγ receptor target and their anti-diabetic activities evaluated. It was observed that three compounds 4e, 4f and 4g showed significantly good in vitro anti-diabetic activity in comparison to pioglitazone as reference drugs. Compound 4g was found to be the most active candidate in lowering blood glucose level and exhibited higher glucose uptake than the reference drug Pioglitazone. The structure-activity relationship and molecular docking analysis revealed that the carboxylate group could interact with Arg 288 and was favorable for interaction with the residues in PPARγ binding site and Compound 4g obtained the best docking score which was equal to -9.6 kcal/mol and able to score even better than the reference PPARγ agonist pioglitazone (-9.3 kcal/mol). The rhodanine molecules based on this series have the potential to provide unique and effective clinical opportunities for treatment of diabetes.
Figure-1: Compound 4g binding mode inside the PPARγ active site; A) Compound 4g (orange sticks) is aligned on the 1WM0 co-crystallized ligand (blue sticks) along with the rosiglitazone bioactive conformation (red sticks); B) Compound 4g binding mode inside the PPARγ active site. The picture was generated by MOE. Hydrogen bonding is shown as orange dotted lines.
Recent Publications
- Shaikha S Al Neyadi, Alaa A Salem, Abdou Adem, Naheed Amir and Ibrahim M Abdou (2017) Synthesis, in vitro biological evaluation of new pyrimidines as Glucagon-Like peptide-1 Receptor Agonists. Bioorganic & Medicinal Chemistry Letters; 27(22): 5071-5075.
- Shaikha S Al Neyadi, Alaa A Salem, Mohammad A Ghattas, Noor Atatreh and Ibrahim M Abdou (2017) Antibacterial Activity and Mechanism of Action of the Benzazole Acrylonitrile-Based Compounds: in vitro, spectroscopy and docking studies. European Journal of Medicinal Chemistry; 136: 270-282.