D-Captopril

D-Captopril is a NDM-1 inhibitor and a competitive BlaB inhibitor, with an IC₅₀ value of 21.8 µM against NDM-1 and a K i of 70-100 µM against BlaB. D-Captopril synergistically reduces the minimum inhibitory concentration of Meropenem against NDM-1-expressing bacteria. D-Captopril binds to BcII via its thiolate sulfur atom and carboxylate group, altering metal ion occupancy and modulating Cd 2+ binding affinity. D-Captopril can be used in the research of neonatal meningitis, sepsis and bacterial infections ^{[1] [2] [3]}.

In Vitro, D-Captopril (2 mM; ~5 weeks) binds to BlaB of *Chryseobacterium meningosepticum* by inserting its sulfhydryl group between the two active-site Zn2+ ions of BlaB and displacing the catalytic hydroxyl group. It acts as a competitive inhibitor of BlaB at neutral pH, with a Ki of 70-100 μM^[1]. D-Captopril inhibits the enzymatic activity of purified wild-type NDM-1 through interactions with active site residues and stabilized water networks, with an IC₅₀ value of 21.8 μM^[2]. D-Captopril (8-32 mg/L) acts synergistically with Meropenem at the concentration of 32 mg/L, reducing the MIC of Meropenem against E. coli DH5α expressing NDM-1 from 8 mg/L to 4 mg/L, whereas no synergistic effect is observed at the concentration of 8 mg/L^[2].

References:
[1]. García-Saez I, et al. The 1.5-A structure of Chryseobacterium meningosepticum zinc beta-lactamase in complex with the inhibitor, D-captopril. J Biol Chem. 2003;278(26):23868-23873.
[2]. Ma G, et al. Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors. Bioorg Med Chem. 2021;29:115902.
[3]. Heinz U, et al. Coordination geometries of metal ions in d- or l-captopril-inhibited metallo-beta-lactamases. J Biol Chem. 2003;278(23):20659-20666.