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QSAR studies for some thiazolidine-2,4-dione derivatives as PIM-2 kinase inhibitors

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Abstract

Quantitative structure–activity relationship (QSAR) studies were performed on a series of 21 thiazolidine-2,4-dione derivatives to find the structural requirements for PIM-2 kinase inhibitory activity by two-dimensional (2D-QSAR), group-based (G-QSAR) and three-dimensional (3D-QSAR) studies. In the present study, widely used technique viz. stepwise forward–backward (SW-FB) has been applied for the development of 2D- and G-QSAR as variable selection method. The statistically significant best 2D-QSAR model was developed by partial least squares regression (PLSR) having r 2 = 0.78, q 2 = 0.63 with pred_r 2 = 0.78. The statistically significant best G-QSAR model was developed by PLSR method having r 2 = 0.89, q 2 = 0.79 and pred_r 2 = 0.82. The 3D-QSAR studies were performed by k-nearest neighbor molecular field analysis along with genetic algorithm method which showed q 2 = 0.64 and pred_r 2 = 0.94. A docking study revealed the binding orientations of these inhibitors at active site amino acid residues (PHE 43, ASP 124, ASP 182 and GLU 83) of PIM-2 enzyme (PDB ID: 3IWI). The results of this study may be useful to (medicinal) chemists to design more potent thiazolidine-2,4-dione analogs as PIM-2 kinase inhibitors.

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Acknowledgments

The authors gratefully acknowledge Indian Council of Medical Research (ICMR), New Delhi, for providing Senior Research Fellowship (SRF) to Mr. Vivek Asati (SRF No. 45/28/2013-PHA/BMS).

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  1. Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India

    Vivek Asati & Sanjay K. Bharti

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  1. Vivek Asati
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  2. Sanjay K. Bharti
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Correspondence to Vivek Asati.

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Asati, V., Bharti, S.K. QSAR studies for some thiazolidine-2,4-dione derivatives as PIM-2 kinase inhibitors. Med Chem Res 25, 1329–1339 (2016). https://doi.org/10.1007/s00044-016-1577-z

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  • DOI: https://doi.org/10.1007/s00044-016-1577-z

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