Novel pyrimidine derivatives of rhodanine as PPARγ agonist | 11599
Drug Designing: Open Access

Drug Designing: Open Access
Open Access

ISSN: 2169-0138

Novel pyrimidine derivatives of rhodanine as PPARγ agonists: Design, synthesis, molecular docking and glucose uptake

5th Annual Congress on Chemistry in Drug Discovery & Designing

April 16-17, 2018 Dubai, UAE

Shaikha S Al Neyadi, Abdu Adem, Naheed Amir, Mohammad A Ghattas, Noor Atatreh, Alaa A Salem and Ibrahim M Abdou

United Arab Emirates University, UAE
Al Ain University of Science and Technology, UAE

Posters & Accepted Abstracts: Drug Des

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-2 diabetes mellitus and diabetic complications, respectively. Chemical modifications of these heterocycles 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 PPAR�?³ 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 PPAR�?³ 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 PPAR�?³ 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. Recent Publications 1. 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. 2. 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

Biography :

Shaikha S Al Neyadi has obtained her PhD degree in 2016 from United Arab Emirates University, UAE. Her current research interest focus is on design and synthesis of bioactivity of novel derivatives as anti-diabetic and anti-bacterial drugs.