A group of 33 carboxylic acid related chemicals were tested for histone deacetylase (HDAC) inhibitor activity to learn which molecular structures are most active. Histone acetylation and deacetylation are important for gene expression.
Deacetylation causes condensation of chromatin of the DNA. With condensation, information from the DNA is more difficult to access. Inhibition of deacetylation is believed to be beneficial in neurodegeneration, hereditary diseases, inflammatory diseases and cancers. Inhibition results in increased acetylated histones (proteins). This alters 7-10% of genes by normalizing cell growth, increasing differentiation and causing apoptosis of abnormal cells.
Butyric acid, phenylbutyric acid and valproic acid are caffeic acid derivatives which have HDAC inhibitor activity. Of the chemicals tested, curcumin and chlorogenic acid (two caffeic acid derivatives) were most similar to sodium butyrate, a known strong HDAC inhibitor. Both chlorogenic and caffeic acids are coffee polyphenols which are, also, DNA methylation inhibitors.
DNA methylation and histone acetylation are involved in epigenetic gene regulation. Curcumin and chlorogenic acid are active at micromolar levels. Caffeic acid is active at millimolar levels.
Attempts were made to modify the structure of a number of HDAC chemicals. None resulted in improved HDAC inhibition activity.
CONCLUSION: Chlorogenic acid and curcumin have potent HDAC inhibition activity. Caffeic acid has moderate HDAC inhibitory activity. These may provide new treatments for neurodegenerative, hereditary diseases, inflammatory diseases and cancer.
NOTE: Epigenetics is the study of factors which can alter the expression of DNA and alter genetics. Read about histone modification as a mechanism of epigenetics.
To read the author’s abstract of the article click on the link to the author’s title of the article above.