Synthesis and preliminary antimicrobial activities of new arylideneamino-1,3,4-thiadiazole-(thio/dithio)-acetamido cephalosporanic acids

Molecules. 2012 Jan 19;17(1):1025-38. doi: 10.3390/molecules17011025.

Abstract

New derivatives of 7-aminocephalosporanic acid 1-8 were synthesized by acylation of the 7-amino group of the cephem nucleus with various arylidinimino-1,3,4-thiadiazole-thio(or dithio)-acetic acid intermediates 3a-d and 5a-d, respectively, so the acyl side chains of these new cephalosporins contained a sulfide or disulfide bond. This unique combination of a Schiff base with the sulfide or disulfide bonds in the acyl side chain afforded new cephalosporins of reasonable potencies, some of which were found to possess moderate activities against the tested microorganisms. Their chemical structures were characterized by ¹H-NMR, IR spectroscopy and elemental microanalysis. Preliminary in vitro antimicrobial activities of the prepared cephalosporins were investigated using a panel of selected microorganisms. Results indicated that the newly synthesized cephalosporins containing disulfide bonds (compounds 5-8) exhibited better activities against Staphylococcus aureus and Escherichia coli. The cephalosporins cross-linked by a sulfide bond (compounds 1-4) showed a slight change in antimicrobial activities when compared with that of the reference cephalosporin (cephalexin).

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Cephalosporins / chemical synthesis*
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacology
  • Disulfides / chemical synthesis
  • Disulfides / chemistry
  • Disulfides / pharmacology
  • Escherichia coli / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Spectrophotometry, Infrared
  • Staphylococcus aureus / drug effects
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology
  • Thioacetamide / analogs & derivatives
  • Thioacetamide / chemical synthesis
  • Thioacetamide / pharmacology
  • Transition Temperature

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Disulfides
  • Schiff Bases
  • Thiadiazoles
  • Thioacetamide