Synthetic Optimization of Zinc Metallo-β-Lactamase Inhibitor
β-lactams antibiotics are commonly prescribed drug classes used in the management and treatment of many bacterial infections. These drugs have drastically changed the fight against numerous diseases and resulted in an expenditure of $15 billion annually. However, a major public health challenge to β-lactam antibiotics is the resistance mechanism developed by bacteria, rendering the treatment ineffective. The mode of resistance is developed by the expression of β-lactamase which enzymatically catalyzes the cleavage of the β-lactam ring. The focus of my research is a particular class of β-lactamase known as metallo-β-lactamase (MBL), found in strains of pneumonia, which requires Zn (II) for its activity. Currently, there are no FDA-approved MBL inhibitors (MBLi), and QPX7728 (Qpex Biopharma, Inc) is the only inhibitor in clinical trials. As such, the discovery of novel classes of MBL inhibitors remains an active area of research. The main objective of my project is to synthesize a series of pyrithione analogues and explore their structure-activity relationship (SAR) against MBLs such as NDM-1 and VIM-2.