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Structure guided inhibitor designing of CDK2 and discovery of potential leads against cancer

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Abstract

On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. The binding affinities are represented in glide score. (5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I1), (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were selected for synthesis and biological testing based on vital interactions. (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide(I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were proved to be active against MCF-7 and HeLa cell lines.

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Authors and Affiliations

  1. Department of S & H (Computer Applications), Sathyabama University, Chennai, India

    Arun Kumar V.A

  2. SVN College of Engineering, Mavelikkara, Kerala, India

    Keshav Mohan

  3. Gokaraju Rangaraju Institute of Engineering & Technology, Hyderabad, India

    Syed Riyaz

Authors
  1. Arun Kumar V.A
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  2. Keshav Mohan
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  3. Syed Riyaz
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Correspondence to Arun Kumar V.A.

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V.A, A.K., Mohan, K. & Riyaz, S. Structure guided inhibitor designing of CDK2 and discovery of potential leads against cancer. J Mol Model 19, 3581–3589 (2013). https://doi.org/10.1007/s00894-013-1887-8

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  • DOI: https://doi.org/10.1007/s00894-013-1887-8

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