Structure-activity relationships in the beta-lactam family: an impossible dream.
The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different sensitivities. (2) Some bacteria produce beta-lactamases, enzymes capable of destroying the antibiotics. The rates of the reactions with the beta-lactamases and the target enzymes are not necessarily related. (3) In Gram-negative bacteria, the diffusion rate through the outer membrane varies independently from the two other factors.
Frère
J M
JM
Laboratoire d'Enzymologie et Service de Microbiologie, Université de Liège, Belgium.
Joris
B
B
Varetto
L
L
Crine
M
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases