Abstract
The relationship between the chemical structure and mode of action of piperacillinanalogues (PIPC-analogues) against Pseudomonas aeruginosa was investigated. The antibacterial activities of PIPC-analogues became stronger as the chain length of the alkyl group on the N-4 position in 2, 3-dioxopiperazine when tested in constitutively β-lactamase-producing strain, but not paralleled in wild and β-lactamase-less strains. The outer membrane permeability was hardly affected by the chain length of the alkyl group at the N-4 position. The stability to β-lactamase was stronger with the increase of the number of the carbon atoms of N-4 position. In the binding-affinities to the lethal penicillin-binding proteins (PBPs), compounds PIPC (C-2), C-3 and C-4 showed lower ID50 values than compounds C-1, C-6 and C-8. These results suggested that the stability to β-lactamase was the governing part for the antibacterial activity in constitutively β-lactamase-producing strain, and the binding affinity to lethal PBPs directly contributed to the antibacterial activity in wild and β-lactamase-less strains.
