Antibacterial activity and chemical modifications of PS-5 at the C-3 side chain.
Using PS-5 as starting material, the effects of chemical modification at the C-3 side chain were studied on the antibacterial activity against Gram-positive and Gram-negative bacteria including beta-lactamase-producers. Among 35 side chains tested, 4-pyridylthio showed the highest antibacterial activity against the Gram-positive bacteria, and D-cysteinyl against the Gram-negative microbes. In general, compared with acetamidoethylthio in PS-5, basic side chains showed improved antibacterial activity against the staphylococci and pseudomonads, whereas the antibiotic activity against the Gram-negative bacteria decreased with bulky side chains. The introduction of 6-aminopenicillanate and 7-aminocephalosporanate to the C-3 side chain of carbapenem significantly reduced the antibacterial activity against the beta-lactamase-producing microbes.
Sakamoto
M
M
Sanraku Inc., Central Research Laboratories, Fujisawa, Japan.
Yamamoto
K
K
Isshiki
K
K
Ishikura
T
T
Fukagawa
Y
Y
Yoshioka
T
T
D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013845:Thienamycins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; C016883:PS 5