Compositions of Polyhydroxylated Benzophenones and Methods of Treatment of Neurodegenerative Disorders

Technology

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histones, resulting in increased chromatin compaction and decreased accessibility to transcription. Among them, HDAC1 plays a critical role in the maintenance of DNA integrity and suppression of aberrant cell cycle re-entry in neurons. The polyhydroxylated benzophenone compounds described in this invention activate HDAC1, increasing its deacetylase activity. This enhanced activity promotes chromatin organization and DNA repair, thereby reducing DNA damage and neuronal loss, which contributes to a neuroprotective effect for the treatment of neurodegenerative diseases. 

Problem Addressed

Neurodegenerative disorders such as Alzheimer’s Disease have been linked to a deficiency in HDAC1 activity. Previous studies have shown that reduced HDAC1 activity leads to key features of neurodegenerative pathology. Additionally, research has shown that that HDAC1 activation has a neuroprotective effect, demonstrating the therapeutic potential for HDAC1 as a drug target. To address this need, MIT researchers have identified the polyhydroxylated benzophenone compounds disclosed herein as small-molecule activators of HDAC1. 

Advantages

• Selective activation of HDAC1 for neuroprotection
• Novel chemical scaffold for drug development
• Broad therapeutic potential for neurological diseases including neurodegenerative diseases, psychiatric disorders, and cognitive disorders