Synthesis and preliminary antimicrobial evaluation of new 7-(N-pyrrolyl) derivatives of cephalosporins.
A series of seven new cephalosporins was prepared for preliminary microbiological evaluation by N-acylation of 7-aminocephalosporanic acid with substituted N-pyrrolylcarboxylic acids via mixed anhydrides. The chemical structure of the compounds were confirmed by IR, 1H-NMR and mass spectral data. The 7-(N-pyrrolyl) cephalosporin derivatives were tested in vitro by the disc diffusion method upon 3 strains and subsequent determination of the minimal inhibitory concentration (MIC) of the most active ones upon 29 strains. The products of the series exhibited antibacterial activity. They showed selective potency against gram-positive and were practically inactive against gram-negative microorganisms. The compound 3-[(acetyloxy)methyl]-7-([2-[3-(ethoxycarbonyl)-2-methyl-5-phenyl-1H-1-pyrrolyl]acetyl]amino)-6-oxo-7,7a-dihydro-2H,6H-aceto[2,1-b][1,3]thiazine-4-carboxylic acid (4a) was outlined as more active than the reference cefazolin (CAS 23325-78-2) in regard to S. pyogenes and some strains of S. aureus, the MIC of 4a against S. pyogenes were at least 4-fold lower. The toxicological evaluations of the starting N-pyrrolylcarboxylic acids showed no acute toxicity.
Bijev
Atanas
A
University of Chemical Technology and Metallurgy, Sofia, Bulgaria. a.bijev@uctm.edu
Nankov
Atanas
A
Keuleyan
Emma
E
Markovska
Rumiana
R
Daneva
Elitsa
E
D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002855:Chromatography, Thin Layer; D003470:Culture Media; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003470:Culture Media; D007202:Indicators and Reagents; D011758:Pyrroles