Antipseudomonal Activity of α-Sulfoaminopenicillins

摘要

A series of penicillins characterized by the presence of a sulfoamino or a modified sulfoamino group in the side chain was subjected to in vitro antimicrobial screening tests. Although the most potent members of the series were less active than benzylpenicillin against gram-positive bacteria and comparably active against most gram-negative bacteria, they were, on the average, 8 to 16 times more effective against strains of Pseudomonas aeruginosa. In other comparative laboratory tests against P. aeruginosa, these compounds were about as active as carbenicillin and four to eight times more active than ampicillin. An examination of structure-activity relationships indicated that maximal potency was obtained with penicillins having an α-(aromatic or heteroaromatic)-α-sulfoaminoacetamido side chain. The compound with an α-phenyl group was comparable in activity to those having an α-(2- or 3-thienyl) group, whereas any modification in position or structure of the α-sulfoamino group reduced activity. Results of studies with a cell-free P. aeruginosa β-lactamase suggest that the marked inhibitory effects of α-sulfoamino penicillins for P. aeruginosa can be attributed, at least in part, to their high degree of resistance to this enzyme. Some derivatives, however, had weak antipseudomonal activity, despite possessing a high degree of β-lactamase resistance.