Comparative Evaluation of the Effectiveness of Biocatalytic Synthesis and Antibacterial Activity of Known Antibiotics and “Chimeric” Cephalosporin Compounds

Abstract

The processes of biocatalytic synthesis of cefamandole and cefazoline, as well as four “chimeric” cephalosporins carrying functional groups of these antibiotics in the C3 or C7 position of β-lactam, were carried out using immobilized cephalosporin-acid synthetase under mild standard conditions. A higher efficiency of biocatalytic acylation of β-lactams with a 1(H)-tetrazolylacetic acid residue was demonstrated compared to acylation with mandelic acid residue. The chemical structure of the obtained compounds was confirmed using the HPLC-MS method. The possibility of using directly reaction mixtures for evaluating the antibacterial activity of the compounds synthesized without isolating the target products is demonstrated. The activity of the obtained cephalosporins against twelve microorganisms belonging to the genera Enterococcus, Acinetobacter, Serratia, Pseudomonas, Staphylococcus, and Escherichia was evaluated by the method of diffusion into agar. The activity of synthesized “chimeric” cephalosporins against four microorganisms was found: Escherichia coli VKPM B-6695, Staphylococcus aureus VKPM B-6646, Staphylococcus aureus VKPM B‑8171, and Staphylococcus epidermidis VKPM B-12635.