Synthesis, Biological Screening and <I>in Silico</I> Studies of Chalcone Based Novel Phenyl Urea Derivatives as Potential Antihyperglycemics

Abstract

Aim : Current work was aimed to explore the effect of synthesized novel chalcone based1-(4-methoxyphenyl)-3-{4- [(2E)-3-phenylprop-2-enoyl] phenyl} ureaderivatives, on adult male Wister rats in an experimental model of type 2 diabetes. Methods : Type 2 Diabetes was induced in overnight fasted rats by a high fat diet followed by a single intraperitoneal injection of low dose streptozotocin (35mg/kg body weight) leading to hyperglycemia and considerable augmentation in blood urea nitrogen and creatinine levels. Treatment with compounds 2(a-d) and 3(a-c)(dose; 30mg/kg) continued for 28 days followed by oral glucose tolerance test. Docking studies of synthesized compounds with ligand binding domain of the human peroxisome proliferator activated receptor gamma-2(2PRG) were performedto correlate the antihypergycemic activity for possible mode of action. Result : Oral administration of compounds 2(a-d) and 3(a-c)in 35mg/kg for 4 weeks reduced blood glucose level significantly by 68-71% and 71-75% respectively comparable to that of glipizide(80%) in a dose of 1mg/kg/day coupled with significant reduction (p≤0.05) in the increased blood urea nitrogen and serum triglyceride level. Compound 2c have been found most active on the PPAR gamma receptor displaying docking score (-21) comparable to reference ligands Rosiglitazone and pioglitazone. Conclusion : This observation indicates that chalcone based novel phenylureas have the potential to be an effective antihypergycemic agent with probable PPAR gamma agonistic action.