Disulfiram as a potent metallo-β-lactamase inhibitor with dual functional mechanisms

Abstract

We report a promising NDM-1 inhibitor, disulfiram, which can covalently bind to NDM-1 by forming an S–S bond with the Cys208 residue. Its copper-containing metabolite in vivo, Cu(DTC)₂, also inactivated NDM-1 through oxidizing the Zn(II) thiolate site of the enzyme, therefore exhibiting dual functional inhibitory potential against B1 and B2 subclass MβLs.