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Advances in Bioinformatics
Volume 2014 (2014), Article ID 812148, 11 pages
Research Article

Ligand Based Pharmacophore Modeling and Virtual Screening Studies to Design Novel HDAC2 Inhibitors

Department of Chemistry, Sathyabama University, Jeppiaar Nagar, Chennai 600119, India

Received 11 July 2014; Revised 8 October 2014; Accepted 22 October 2014; Published 26 November 2014

Academic Editor: Gilbert Deleage

Copyright © 2014 Naresh Kandakatla and Geetha Ramakrishnan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Histone deacetylases 2 (HDAC2), Class I histone deacetylase (HDAC) family, emerged as an important therapeutic target for the treatment of various cancers. A total of 48 inhibitors of two different chemotypes were used to generate pharmacophore model using 3D QSAR pharmacophore generation (HypoGen algorithm) module in Discovery Studio. The best HypoGen model consists of four pharmacophore features namely, one hydrogen bond acceptor (HBA), and one hydrogen donor (HBD), one hydrophobic (HYP) and one aromatic centres, (RA). This model was validated against 20 test set compounds and this model was utilized as a 3D query for virtual screening to validate against NCI and Maybridge database and the hits further screened by Lipinski’s rule of 5, and a total of 382 hit compounds from NCI and 243 hit compounds from Maybridge were found and were subjected to molecular docking in the active site of HDAC2 (PDB: 3MAX). Finally eight hit compounds, NSC108392, NSC127064, NSC110782, and NSC748337 from NCI database and MFCD01935795, MFCD00830779, MFCD00661790, and MFCD00124221 from Maybridge database, were considered as novel potential HDAC2 inhibitors.