Anna M.

Central Nervous System Drugs and the Inhibition of Histone Deacetylases

Mentors: David Olson, Michel Weiwer, Flo Wagner

Histone deacetylases are enzymes that remove acetyl groups from proteins, and some HDACs (such as HDAC6) are implicated in neurodegenerative disease. Anna and her mentors designed & synthesized four chemical compounds, in hopes of generating HDAC inhibitor compounds, as these could potentially help treat neurodegenerative disorders. Anna tested three of these new compounds on rat cortical neurons, to determine how potent and selective they function as HDAC6 and HDAC8 inhibitors.

Anna also conducted a literature search to identify a set of rules to define the likelihood of a chemical compound being able to penetrate the blood brain barrier, an important characteristic of CNS drugs. By analyzing the properties of 60 known FDA-approved CNS drugs, Anna found that the number of hydrogen bond donors is a property that predicts the ability of a drug to reach the brain. Anna also noted that most CNS drugs were approved in the 1990s, and since, there has a been a slow decline in the number of newly-approved CNS drugs.



Anna – a senior at Belmont High School – synthesized, tested and researched several chemical compounds, to determine which properties predict if they will be good CNS drugs.