Activation of the GLP-1 receptor by chloropyrimidine derivatives

Results in Chemistry

Mohammad A Ghattas¹  Noor Atatreh²  Naheed Amer³  Ibrahim M. Abdou⁴  Shaikha S. AlNeyadi⁵  Alaa A. Salem⁶  Abdu Adem⁶ 

[1] Corresponding authors at: Department of Chemistry, College of Science, UAE University Al-Ain, 15551, UAE (Ibrahim M. Abdou);Department of Pharmacology and Therapeutics, College of Medicine Health and Sciences, UAE University Al-Ain, 17666, UAE and Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, UAE (A. Adem).;Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, UAE;College of Pharmacy, Al Ain University, Abu Dhabi 112612 UAE;Department of Chemistry, College of Science, UAE University Al-Ain, 15551, UAE;Department of Pharmacology and Therapeutics, College of Medicine Health and Sciences, UAE University Al-Ain, 17666, UAE;

关键词: Synthesis;    Type 2 diabetes;    GLP-1;    Pyrimidine;    Docking;   

DOI  :  

来源: DOAJ

【 摘 要 】

The anti-diabetic activities of a series of chloropyrimidine derviatives 2a-k and 4a-k were investigated after they were designed, synthesized, and docked against the GLP-1 receptor target. In comparison to exenatide, which was utilized as a reference drug, the three chloropyrimidine synthesized compounds 2c, 2f and 4c exhibited potent in vitro and in vivo antidiabetic activities. Interestingly, compounds 2c, 2f and 4c showed to be the most effective in lowering blood glucose levels and led to even higher glucose uptake than the reference drug, exenatide. Consistent with the in vitro and in vivo data, compounds 4c and 2f had the lowest docking energy scores (Glide-XP score = 5.1 kcal/mol) and the greatest ligand efficiency score (> − 0.40 kcal/mol) among all docked compounds. These findings give up new possibilities for the development of high-efficacy compounds to treat hyperglycemia.

【 授权许可】

Unknown