title: Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies.
abstract: In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor-enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor.
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Medical Biology, 06100 Sihhiye, Ankara, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Bora-Tatar
authors.forename: Didem
authors.initials: D
authors.lastname: Dayangaç-Erden
authors.forename: Ayhan S
authors.initials: AS
authors.lastname: Demir
authors.forename: Sevim
authors.initials: S
authors.lastname: Dalkara
authors.forename: Kemal
authors.initials: K
authors.lastname: Yelekçi
authors.forename: Hayat
authors.initials: H
authors.lastname: Erdem-Yurter
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding
chemical_list: D002109:Caffeic Acids; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D002726:Chlorogenic Acid; D006655:Histone Deacetylases; D003474:Curcumin; C040048:caffeic acid