Ligand and structure based pharmacophore modeling to facilitate novel histone deacetylase 8 inhibitor design.
Over expression of histone deacetylases (HDACs) leads to the suppression of various gene expressions including cancer suppressor gene. Thus, novel inhibitors of these enzymes can be a valid method to treat cancers. To facilitate the discovery of novel HDAC8 inhibitors, pharmacophore models were generated using ligand and receptor based approaches and validated with a database of active and inactive compounds. These validated pharmacophores have effectively been used in search of three databases and final hits were subjected to molecular docking using GOLD 4.1 program. Hit compounds that scored high GOLD fitness scores and showed interactions with catalytically important residues and metal ions were considered. Finally, three compounds have been reported as novel virtual leads to design potent HDAC8 inhibitors.
Thangapandian
Sundarapandian
S
Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Gyeongsang National University (GNU), 900 Gazwa-dong, Jinju 660-701, Republic of Korea.
John
Shalini
S
Sakkiah
Sugunadevi
S
Lee
Keun Woo
KW
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D008024:Ligands; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases