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3D-QSAR study of tyrosine and propanoic acid derivatives as PPARα/γ dual agonists using CoMSIA

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Abstract

The peroxisome proliferator-activated receptors (PPARs) have increasingly become attractive targets for developing novel therapeutics for Type 2 Diabetes. Three dimensional-quantitative structure–activity relationship approach has been applied to a series of α-substituted 3-phenylpropanoic acid and tyrosine derivatives, reported as PPARα/γ dual agonists. Comparative molecular similarity indices analysis has been employed in correlating pharmacological data available for single enantiomer at individual receptor subtype. Three models: PPARα, PPARγ and PPARdual-model, using sum of individual activities as dependent parameter, are developed with statistically significant r 2cv  > 0.5 and r 2ncv  > 0.9 and lower values of standard error of estimation. This information can be used to design and prediction of enantioselective novel PPAR agonists. Activities of two sets of designed new molecules have also been predicted using generated models.

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Acknowledgments

We greatly acknowledge the financial support from IndSwift Labs. Ltd. SAS Nagar Mohali for the ISLL-Punjabi University Collaborative Research, and providing the research fellowship to two of the authors VK and PG.

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Authors and Affiliations

  1. Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala, Punjab, 147002, India

    Raman K. Verma, Vijay Kumar & Prithwish Ghosh

  2. Ind-Swift Laboratories Limited (Research and Development Centre), Plot No. E-5, Industrial Area, Phase-2, S.A.S. Nagar, Mohali, Punjab, India

    Lalit K. Wadhwa

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  1. Raman K. Verma
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  2. Vijay Kumar
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  3. Prithwish Ghosh
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  4. Lalit K. Wadhwa
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Correspondence to Raman K. Verma.

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Verma, R.K., Kumar, V., Ghosh, P. et al. 3D-QSAR study of tyrosine and propanoic acid derivatives as PPARα/γ dual agonists using CoMSIA. Med Chem Res 22, 287–302 (2013). https://doi.org/10.1007/s00044-012-0003-4

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  • DOI: https://doi.org/10.1007/s00044-012-0003-4

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