Pyrrolobenzodiazepine (PBD) dimer SG 2057 has highly efficient interstrand cross-linking activity at concentrations that can be readily attained in vivo and are well below the toxic threshold. This and other agents are being assessed for activity as antibacterial agents. Initial Minimum Inhibitory Concentration (MIC) results indicate that PBD dimers are very active against Gram-positive pathogens. They have a reduced activity against Gram-negatives, probably due to the barrier function of the other membrane. Further, SG 2057 exhibits potent bactericidal activity against MRSA and VRE. It also induces profound morphological changes at inhibitory concentrations.
The focus of Project P 080 is to obtain Proof of Concept in two models of MRSA infection - the peritonitis and the neutropenic model.
