Histone Deacetylase Inhibitors as Multitarget Ligands: New Players in Alzheimer's Disease Drug Discovery?

Histone Deacetylase Inhibitors as Multitarget Ligands: New Players in Alzheimer's Disease Drug Discovery? ChemMedChem. 2019 Apr 08;: Authors: Milelli A, De Simone A Abstract Molecules able to interfere with epigenetic mechanisms, aimed at controlling change in gene expressions without altering the structure of DNA, represent one of the major breakthroughs in drug discovery. Among these agents, histone deacetylases inhibitors (HDACIs) are of highly importance. Indeed, HDACIs control gene expression by modulating the acetylation status of histone proteins. Furthermore, they modulate the activity of cytoplasmic non-histone proteins. Due to the role of HDACs in neurodevelopment, memory formation and cognitive processes, HDACIs has been proposed as innovative agents in the context of neurodegenerative conditions such as Alzheimer's disease (AD). Nevertheless, due to issues related to their mechanisms of action and to the complex nature of AD, HDACIs have been recently employed in the design of novel Multitarget agents. Herein, we will provide the rationale of the design strategy and discuss about the recent efforts to design HDACIs-based Multitarget agents as potential disease-modifying entities. PMID: 30958639 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research