Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
- 40 Downloads
The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor.
KeywordsKnoevenagel reaction Molecular modeling PPARγ Structure–activity relationships Type 2 diabetes TZDs
One of the authors, RNC is thankful to Mr. Awatar singh and Manish kumar, SAIF, Punjab University, Chandigarh, for providing spectral data of all the synthesized compounds. The author is also greatly thankful to management of Ind-Swift laboratory Ltd., for providing all necessary facility to carry out this research work.
- 2.De-Fronzo RA (1992) Diabetologia 35:389.hGoogle Scholar
- 9.Silink M, Tuomilehto J, Mbanya JC, Venkat Narayani KM, Fradkin J, Roglic G (2010) A prioritized research agenda for prevention and control of noncommunicable diseases. World Health Organization, GenevaGoogle Scholar
- 12.Harrichund P, Naicker S, Raal FJ (2008) J Endocrinol 13:3Google Scholar
- 26.Grillier-Vuissoz I, Mazerbourg S, Boisbrun M, Kuntz S, Chapleur Y, Flament S (2012) J Carcinog Mutagen S8:002Google Scholar
- 28.Patel KP, Joshi HM, Majmudar FD, Patel VJ (2013) J Med Sci 2:6Google Scholar