Characteristics of experimental MBL inhibitors

Inhibitor typeRepresentative compoundEnzyme testedAffinitya (μM)Demonstrable potentiationReference
Thioester derivativeMorpholinoethanesulfonic acidCcrAKi 23NDb44
SB217782/8018/9158L1IC50 <1.9ND119
SB214752L1IC50 2ND119
Biphenylmethyl derivativesIMP-1IC50 0.0004Potentiation with E. coli expressing IMP-1170
CcrAIC50 180ND
Trifluoromethyl alcohold-Alanine derivativeL1Ki 1.5ND182
ThiolMercaptoacetic acidIMP-1Ki 0.23ND56
Mercaptopropionic acidIMP-1Ki 0.19ND
2′-Mercaptoethyl-derivativeBCIIKi 70ND18
Thiobenzoate derivativeIMP-1IC50 0.0004ND57
CcrAIC50 180ND
2-para-Thiomandelic acidBCIIKi 0.21ND101
Quinoline C45HIMP-1IC50 1.2ND71
VIM-2IC50 1.1ND
Sulfonyl hydrazone2-Naphthyl derivativesIMPIC50 1.6ND160
Tricyclic productSB238569BCIIKi 79ND122
IMP-1Ki 17No potentiation found with P. aeruginosa (IMP-1)
CcrAKi 3.48-fold synergistic effect with B. fragilis (CcrA)
2S-3S disubstituteIMP-1IC50 >0.21ND171
Biphenyl tetrazoleL161, 189CcrAIC50 0.30Possessed activity alone and potentiation with imipenem against B. fragilis (CcrA)170
Cysteinyl peptided-Phenylalanine derivativeBCIIKi 3.0ND17
1-β-Methyl-carbapenemJ-110, 441IMP-1Ki 0.0037Potentiation with imipenem for S. marcescens (IMP-1) and for some P. aeruginosa (IMP-1) strains104
CcrAKi 0.23ND
L1Ki 1.0ND
J111, 225IMP-1Ki 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
ThioxocephalosporinThioacidBCIIKi 96ND173
  • a IC50, concentration of inhibitor required to inhibit 50% of MBL activity.

  • b ND, no data.