Inhibitory activity and resistance to hydrolysis by beta-lactamases of some (D,L)-7-(alpha-fluoroacylamino)cephalosporins.
The synthesis of a series of (D,L)-7-(alpha-fluoroacylamino)-cephalosporanic acids are described. In vitro antimicrobial activity was determined in comparison with the corresponding non-fluorinated compounds. None of them were found to be better than clinically used cephalosporins. Resistance to and inhibition of beta-lactamases from gram-negative organisms were also determined. All the fluorinated derivatives were found to be as resistant to hydrolysis by Escherichia coli R+TEM beta-lactamase as the corresponding non-fluorinated compounds, but resulted more resistant (from 2.3 to 61.2 times) to Enterobacter cloacae 214 beta-lactamase. Title compounds were also found to be better inhibitors of E. cloacae 53 and E. cloacae 214 beta-lactamases than the related non-fluorinated cephalosporins.
D001419:Bacteria / Q000187:drug effects; D002510:Cephalosporinase / Q000378:metabolism*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000201:enzymology; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D002510:Cephalosporinase; D001618:beta-Lactamases