Ligand Based Pharmacophore Modeling and Virtual Screening Studies to Design Novel HDAC2 Inhibitors
Autor: | Geetha Ramakrishnan, Naresh Kandakatla |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Virtual screening
Quantitative structure–activity relationship Article Subject Chemistry Biomedical Engineering Protein Data Bank (RCSB PDB) Computational biology Ligand (biochemistry) Bioinformatics Biochemistry Genetics and Molecular Biology (miscellaneous) Computer Science Applications lcsh:Biology (General) Lipinski's rule of five Histone deacetylase Pharmacophore lcsh:QH301-705.5 lcsh:Statistics lcsh:HA1-4737 Discovery Studio Research Article |
Zdroj: | Advances in Bioinformatics, Vol 2014 (2014) Advances in Bioinformatics |
ISSN: | 1687-8035 1687-8027 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |