Cephabacin F1

Cephabacin F group antibiotics with a 7-formylamino substituent showed antibacterial activity against a wide variety of bacteria including beta-lactamase-producing clinical isolates and anaerobic bacteria. Cephabacin H group antibiotics without the substituent showed more potent activity against Gram-positive bacteria than cephabacin F group antibiotics, but were not active against Gram-negative bacteria producing beta-lactamases. Cephabacin F group antibiotics were highly resistant to hydrolysis by various types of beta-lactamases and showed strong inhibitory activity against a cephalosporinase of Proteus vulgalis GN 4413 due to the 7-formylamino substituent. Mode of action of cephabacin F1 and H1 was examined using Escherichia coli and Bacillus subtilis as the test organisms. They showed strong lytic activity against these organisms and inhibited their peptidoglycan synthesis. Cephabacin F1 had the highest affinity for penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis. Cephabacins showed a protective effect in experimentally infected mice.

The structures of 15 new cephem antibiotics, cephabacin F1-9 and H1-6, were determined by their spectroscopic analyses and decomposition studies. They are consisted of a cephalosporin nucleus and a di, tri or tetrapeptide including a new amino acid which is bound at the position 3 with an ester bond. The components, F1-9, showed unique biological activities by the presence of a formylamino group at the position 7.