TABLE 5.

Characteristics of experimental MBL inhibitors

Inhibitor typeRepresentative compoundEnzyme testedAffinitya (μM)Demonstrable potentiationReference
Thioester derivativeMorpholinoethanesulfonic acidCcrA Ki 23NDb 44
SB217782/8018/9158L1IC50 <1.9ND 119
SB214752L1IC50 2ND 119
Biphenylmethyl derivativesIMP-1IC50 0.0004Potentiation with E. coli expressing IMP-1 170
CcrAIC50 180ND
Trifluoromethyl alcohol d-Alanine derivativeL1 Ki 1.5ND 182
BCII Ki 300ND
ThiolMercaptoacetic acidIMP-1 Ki 0.23ND 56
Mercaptopropionic acidIMP-1 Ki 0.19ND
2′-Mercaptoethyl-derivativeBCII Ki 70ND 18
Thiobenzoate derivativeIMP-1IC50 0.0004ND 57
CcrAIC50 180ND
2-para-Thiomandelic acidBCII Ki 0.21ND 101
Quinoline C45HIMP-1IC50 1.2ND 71
VIM-2IC50 1.1ND
Sulfonyl hydrazone2-Naphthyl derivativesIMPIC50 1.6ND 160
Tricyclic productSB238569BCII Ki 79ND 122
IMP-1 Ki 17No potentiation found with P. aeruginosa (IMP-1)
CcrA Ki 3.48-fold synergistic effect with B. fragilis (CcrA)
2S-3S disubstituteIMP-1IC50 >0.21ND 171
Biphenyl tetrazoleL161, 189CcrAIC50 0.30Possessed activity alone and potentiation with imipenem against B. fragilis (CcrA) 170
Cysteinyl peptide d-Phenylalanine derivativeBCII Ki 3.0ND 17
1-β-Methyl-carbapenemJ-110, 441IMP-1 Ki 0.0037Potentiation with imipenem for S. marcescens (IMP-1) and for some P. aeruginosa (IMP-1) strains 104
CcrA Ki 0.23ND
L1 Ki 1.0ND
BCII Ki 0.83ND
J111, 225IMP-1 Ki 0.188-fold potentiation with imipenem for P. aeruginosa (IMP-1) 105
Penicillin derivativePenicillinate sulfoneL1IC50 0.10Some potentiation evident with piperacillin/tazobactam against E. coli (IMP-1) 25
BCIIIC50 1.4See above
ThioxocephalosporinThioacidBCII Ki 96ND 173
  • a IC50, concentration of inhibitor required to inhibit 50% of MBL activity.

  • b ND, no data.