Cytotoxicity activity model of hydroxamic acid analogues as histone deacetylase (hdac) inhibitors based on docking and pharmacophore 3D QSAR approach

Authors

  • Md. Afroz Alam Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India Author
  • N. Christu Veni Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India Author
  • Ligi George Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India Author
  • Anurupa Devi.Y Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India Author
  • Thalitha Jane. D Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India Author

DOI:

https://doi.org/10.5530/4hwtr050

Keywords:

Histone deacetylases, Hydroxamic acid, Docking, Pharmacophore, QSAR

Abstract

Histone deacetylases (HDACs) enzyme is a promising target for the development of anticancer drugs. The enzyme-bound conformation of Trichostatin A (TSA) in complex with the protein Histone deacetylase was used for a detailed study of the binding site of the protein. 
Hydroxamic acid analogues, the class to which TSA belongs were used for docking and the docked ligands obtained after refinement of docking result were used to build the pharmacophore model. The best 3D QSAR model was obtained by plotting the Experimental IC (Expt. IC ) and 50 50 the Predicted IC (Pred. IC ) and calculating the regression coefficient 50 502 (R ) value for the hypotheses. The value of the regression coefficient for 2 2 both the training sets (R = 0.7098) and the test set (R = 0.9592) were satisfactory. Graphical interpretation and the 3D QSAR model built revealed important structural features of the inhibitors related to the active site of HDACs. The results can therefore be exploited for further design and virtual screening for some novel HDAC inhibitors.

 

 

 

 

Author Biographies

  • Md. Afroz Alam, Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

     

     
  • N. Christu Veni, Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

     

       
  • Ligi George, Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

     

     
  • Anurupa Devi.Y, Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

     

     
  • Thalitha Jane. D, Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

     

     

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Published

2014-06-30

Issue

Vol. 2 No. 2 (2012)

Section

Articles

How to Cite

Cytotoxicity activity model of hydroxamic acid analogues as histone deacetylase (hdac) inhibitors based on docking and pharmacophore 3D QSAR approach. (2014). Asian Journal of Pharmaceutical and Health Sciences, 2(2), 320-327. https://doi.org/10.5530/4hwtr050