Price K E, Chisholm D R, Leitner F, Misiek M, Gourevitch A
Appl Microbiol. 1969 Jun;17(6):881-7. doi: 10.1128/am.17.6.881-887.1969.
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 alpha-(aromatic or heteroaromatic)-alpha-sulfoaminoacetamido side chain. The compound with an alpha-phenyl group was comparable in activity to those having an alpha-(2- or 3-thienyl) group, whereas any modification in position or structure of the alpha-sulfoamino group reduced activity. Results of studies with a cell-free P. aeruginosa beta-lactamase suggest that the marked inhibitory effects of alpha-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 beta-lactamase resistance.
对一系列在侧链中含有磺氨基或修饰磺氨基的青霉素进行了体外抗菌筛选试验。尽管该系列中最有效的成员对革兰氏阳性菌的活性低于苄青霉素，对大多数革兰氏阴性菌的活性相当，但它们对铜绿假单胞菌菌株的平均效力要高8至16倍。在其他针对铜绿假单胞菌的比较实验室试验中，这些化合物的活性与羧苄青霉素相当，比氨苄青霉素高4至8倍。结构-活性关系研究表明，具有α-（芳基或杂芳基）-α-磺氨基乙酰胺基侧链的青霉素具有最大效力。具有α-苯基的化合物的活性与具有α-（2-或3-噻吩基）的化合物相当，而α-磺氨基的位置或结构的任何改变都会降低活性。对无细胞铜绿假单胞菌β-内酰胺酶的研究结果表明，α-磺氨基青霉素对铜绿假单胞菌的显著抑制作用至少部分可归因于它们对该酶的高度抗性。然而，一些衍生物尽管对β-内酰胺酶具有高度抗性，但抗铜绿假单胞菌活性较弱。
