98248-91-0Relevant academic research and scientific papers
Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components
Wheatley, Nicole C.,Andrews, Katherine T.,Tran, Truc L.,Lucke, Andrew J.,Reid, Robert C.,Fairlie, David P.
supporting information; experimental part, p. 7080 - 7084 (2010/12/25)
Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC 50 10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target.
