STRUCTURE-ACTIVITY RELATIONSHIP OF NEW 2-SUBSTITUTED PENEM ANTIBIOTICS

The antibacterial activities of three new penems with 4-hydroxyprolina mide, L-prolinamide and N-methyl-N-2-propionamide subsituents, respect ively, in position 2 and of their stereoisomers were examined against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium. Es cherichia coil and Pseudomonas aeruginosa, All substituents conferred a broad antibacterial spectrum on the penem moiety. Changes in stereoi somerism selectively improved the activity against E. coli, S. aureus or enterococci. The structure-activity relationships of each compound were discussed in relation to minimum inhibitory concentrations, penic illin-binding protein (PBP) affinity and outer membrane permeability c oefficient in E coli. In this microorganism, PBP 2 was the target for all compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and 2. All antibiotics easily permeated the outer membrane o f E. coli and, within each group of compounds, the penetration rate co rrelated with the antibacterial activity.