Bioorganic & Medicinal Chemistry 2009-07-15

Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies.

Gamze Bora-Tatar, Didem Dayangaç-Erden, Ayhan S Demir, Sevim Dalkara, Kemal Yelekçi, Hayat Erdem-Yurter

文献索引：Bioorg. Med. Chem. 17 , 5219-28, (2009)

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摘要

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.