Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo β-Lactamase-1

Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo-β-lactamase (NDM) enzymes are a contributing element that drive resistance to many β-lactam- and carbapenem-based antimicrobials. Many NDM inhibitors are known, yet none are clinically viable. In this study, we present and characterize a new class of NDM-1 inhibitors based on a pyridine-2,6-dithiocarboxylic acid metal complex scaffold. These complexes display varied and unique activity profiles against NDM-1 in kinetic assays and serve to increase the effectiveness of meropenem, an established antibacterial, in assays using clinical Enterobacteriaceae isolates.