title: Discovery of a series of small molecules as potent histone deacetylase inhibitors.
abstract: A series of small molecules were designed and synthesized based on our previous virtual screening approach, which was performed to discover potent histone deacetylase inhibitors (HDACIs) with novel structures. The derived compounds were tested by Hela cell nucleus extract for enzyme inhibition assay. Tumor cell growth inhibition assays were performed using a series of tumor cell lines. Molecule 4h has the best performance among these compounds with enzyme inhibition IC₅₀ of 0.14 μM and tumor cell growth inhibition IC₅₀ of 1.85 (U937), 2.02 (HL60), 2.67 (K562). Docking studies showed that multiple H-bonds and hydrophobic interactions make 4h binding to the active site of HDAC. 4h has the advantage of low molecular weight, so a variety of structural modifications can be performed in our further studies.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University , Jinan, Shandong , China and.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D018922:HL-60 Cells; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D054852:Small Molecule Libraries; D006655:Histone Deacetylases
keywords: Docking; histone deacetylase inhibitors; phenylglycine; tumor