Inhibition of Acinetobacter-Derived Cephalosporinase: Exploring the Carboxylate Recognition Site Using Novel β-Lactamase Inhibitors.

ABSTRACT: Boronic acids are attracting a lot of attention as β-lactamase inhibitors, and in particular, compound S02030 ( K_i = 44 nM) proved to be a good lead compound against ADC-7 ( Acinetobacter-derived cephalosporinase), one of the most significant resistance determinants in A. baumannii. The atomic structure of the ADC-7/S02030 complex highlighted the importance of critical structural determinants for recognition of the boronic acids. Herein, to elucidate the role in recognition of the R2-carboxylate, which mimics the C₃/C₄ found in β-lactams, we designed, synthesized, and characterized six derivatives of S02030 (3a). Out of the six compounds, the best inhibitors proved to be those with an explicit negative charge (compounds 3a-c, 3h, and 3j, K_i = 44-

SUBMITTER: Caselli E 

PROVIDER: S-EPMC5987196 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature