Jeffy Jeffy

Metallo-β-lactamase (MBL) is a zinc dependent β-lactamase that inactivates a wide range of β-lactam antibiotics. Currently, there is no FDA-approved MBL inhibitor. Since the Sham Lab has recently discovered 8-hydroxyquinoline (8HQ) as a low-cytotoxic, nanomolar MBL inhibitor, the goal of the project is to apply the quantum mechanics/molecular mechanics (QM/MM) method to design and optimize 8HQ to improve its affinity to New Delhi Metallo-β-lactamase type 1 (NDM-1). Here, we have applied quantum mechanics to explore the substitution of various sulfonamides on the electron distribution and utilized the quantum mechanical charges to determine the binding affinity. Additionally, the compounds were synthesized to be tested in a blood assay.