Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist

• Published in: Monatshefte für Chemie 2018-11, Vol.149 (11), p.2069-2084
• Main Authors: Chaturvedi, Radha Nandan, Pendem, Krishnaiah, Patel, Vipul P., Sharma, Mukta, Malhotra, Sunita
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Bladder; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Diabetes; Diabetes mellitus; Edema; Inorganic Chemistry; Molecular docking; Organic Chemistry; Original Paper; Physical Chemistry; Proteins; Side effects; Theoretical and Computational Chemistry; Weight
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-018-2207-x

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 IC 50 values were determined. Among these compounds, six compounds exhibited promising IC 50 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. Graphical abstract