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Samanta, Subir
- Synthesis, Biological Screening and in Silico Studies of Chalcone Based Novel Phenyl Urea Derivatives as Potential Antihyperglycemics
Authors
1 Department of Pharmaceutical Technology, Synthetic and Natural Product Research Laboratory, Jadavpur University, Jadavpur, Kolkata-700032, West Bengal, IN
2 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, IN
Source
Journal of Pharmaceutical Research, Vol 16, No 3 (2017), Pagination: 237-246Abstract
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.
Keywords
Chalcone, Urea, Glucose Tolerance Test, PPAR Gamma.Full Text
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