AC-1370: ITS STABILITY TO β-LACTAMASES, BINDING-AFFINITY TO PENICILLIN-BINDING PROTEINS, AND PROPOSED IN VTVO EFFICACY

Abstract

Investigations were carried out on the stability of AC-1370 to various β-lactamases produced by gramnegative bacteria, on its binding affinity to penicillin-binding proteins (PBPs) of Escherichia coil and Pseudomonas aeruginosa, on the synergy of the drug with the serum complement and/or macrophages, and on its stimulating activity to the defense mechanism of host animals.
It was found that AC-1370 possesses high binding affinity to the Ia and Ib fractions of PBPs of E. coli and P. aeruginosa. Since the Ia and Ib fractions are essential cross-linking enzymes for the murein-biosynthesis, the drug is assumed to show strong bactericidal effect by itself as well as a good synergy of bactericidal effect with the complement and macrophages. The obtained results agreed the above assumption. AC-1370, however, is hydrolyzed by cephalosporinase-type β-lactamases (Richmond's Ia and Ic), especially by Ic, in some extent, so that its antibacterial effect against weakly virulent gram-negative bacilli may be limited.
Stimulation of immune-defense mechanisms in host animals by AC-1370 was weak if any. It is interest to see how the characteristics of AC-1370 reflect the clinical results.