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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Ind-Swift Laboratories Ltd., S.A.S Nagar, Punjab, 160055, India

    Radha Nandan Chaturvedi

  2. Department of Chemistry, School of Sciences, Indira Gandhi National Open University, Maidan Garhi, New Delhi, 110068, India

    Radha Nandan Chaturvedi & Sunita Malhotra

  3. Neuland Laboratories Ltd, Bonthapalle, Telangana, 500043, India

    Krishnaiah Pendem

  4. Sanjivani College of Pharmaceutical Education and Research, Sahajanaandnagar, Shinganapur, Kopargaon, Ahmednagar, Maharashtra, 423603, India

    Vipul P. Patel

  5. CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi, 110020, India

    Mukta Sharma

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  1. Radha Nandan Chaturvedi
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  2. Krishnaiah Pendem
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  3. Vipul P. Patel
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  4. Mukta Sharma
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  5. Sunita Malhotra
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Correspondence to Sunita Malhotra.

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Chaturvedi, R.N., Pendem, K., Patel, V.P. et al. Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist. Monatsh Chem 149, 2069–2084 (2018). https://doi.org/10.1007/s00706-018-2207-x

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  • DOI: https://doi.org/10.1007/s00706-018-2207-x

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