beta-Lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties.
The essential nucleus of beta-lactam antibiotics is the four-membered ring, which can exist fused to form bicyclic ring structures or with moieties alone affixed to the four atoms. Penicillins, penems, carbapenems, and clavams have asymmetric centers at C-5 and C-6; cephalosporins and oxacephems have asymmetric centers at C-6 and C-7. Penicillins, cephalosporins, and monobactams require a beta-acylamino group for antimicrobial activity. Cephalosporins can undergo modification at C-3 and C-7 in both the alpha and beta position. Sulfur can be replaced with oxygen to achieve a more reactive nucleus. The most useful 7-beta-acylamino groups have been a 2-aminothiazolyl and an iminomethoxy or carboxypropyl group. Substitutions on the 7-alpha position increase beta-lactamase stability but decrease activity against staphylococci and Streptococcus pneumoniae. C-3 substitutions, particularly pyridinium groups, increase activity against Pseudomonas aeruginosa and Staphylococcus aureus. Carbapenems possess 6-alkyl substitutions in a trans configuration and inhibit aerobic, anaerobic gram-positive, and gram-negative bacteria. Monobactams are activated by sulfonic, phosphoric, or carboxyl groups, and their properties are related to the C-3-acyl side chain and their beta-lactamase stability to the C-4 grouping. beta-Lactamase inhibitors acylated by beta-lactamases can be penicillanic acid derivatives or clavulanates.
D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000032:analysis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D008997:Monobactams / Q000032:analysis / Q000494:pharmacology; D010406:Penicillins / Q000032:analysis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D008997:Monobactams; D010406:Penicillins; D065093:beta-Lactamase Inhibitors