Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies.
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.
Bora-Tatar
Gamze
G
Hacettepe University, Faculty of Medicine, Department of Medical Biology, 06100 Sihhiye, Ankara, Turkey.
Dayangaç-Erden
Didem
D
Demir
Ayhan S
AS
Dalkara
Sevim
S
Yelekçi
Kemal
K
Erdem-Yurter
Hayat
H
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
D002109:Caffeic Acids; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D002726:Chlorogenic Acid; D006655:Histone Deacetylases; D003474:Curcumin; C040048:caffeic acid