Apr 20th, 1:00 PM - 4:00 PM
Bithionol Sulfone as Potential Carbonyl Reductase Inhibitor
Dr. Mike McCormick
Carbonyl reductase catalyzes the NADPH-dependent reduction of a wide range of carbonyls. CR has been connected to several important processes including quinone detoxification, neuroprotection, prostaglandin metabolism, and anthracycline metabolism. CR reduction of anthracyclines negatively impacts their use in the treatment of cancer in two important ways: drug resistance and cardiotoxicity. Inhibition of CR in conjunction with anthracycline therapy offers the potential to increase the effectiveness of the drugs at lower doses, and to decrease the risk of cardiotoxicity. The goal is to better understand how CR recognizes the molecules to which it binds, be they substrates or inhibitors. With this information, drugs could be designed to control CR with the intention of reducing the risk of cardiotoxicity during anthracycline cancer treatment. Also, as the role of CR is better understood, it may have applications to other drug pathways as well. Currently the lab is testing out analogs of 4-benzoyl pyridine as potential carbonyl reductase inhibitors. The objective is to synthesize bithionol sulfone and then test this compound as a CR inhibitor. The results will further define the binding properties of the enzyme as well as investige new classes of molecules that potentially can serve as inhibitors.