Antimicrobial activity of two antitumour agents and ribonucleotide reductase inhibitors, pyridine-2-carboxaldehyde thiosemicarbazone and the acetate form of its copper(II) chelate.
Some copper chelates have potent antitumour activity, and in some cases also the free ligands have activity in vivo. Yet, little is known about their antimicrobial properties. Copper(II) chelates of the thiosemicarbazones of a-N-heterocyclic carboxaldehydes constitute one important group of such agents, also their ligands having marked antitumour activity. Both the ligands and chelates inhibit ribonucleotide reductase. Some ligands have been or are under clinical trials as antineoplastic agents. I report here a study on the antimicrobial properties of the prototype compounds of this group, pyridine-2-carboxaldehyde thiosemicarbazone and its copper(II) chelate. They were tested against nine microbes, including bacteria (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus lactis), yeasts (Candida albicans and Saccharomyces cerevisiae) and one mold (Aspergillus niger). Two clinical isolates of Bacillus sp. and one reference strain were also studied. Both the ligand and the chelate had marked activity. The ligand displayed considerable activity against all bacteria except for S. lactis, and its activity against E. coli and P. aeruginosa was that high that practical applications might be considued. It was highly active against A. niger and moderately active against C. albicans. The chelate was highly active against S. epidermidis and S. cerevisiae. Both compounds inhibited the clinical isolates markedly. Since some related ligands have been or are in clinical trials on humans or are entering them, their route to clinical use, also as antimicrobials, might be much more straightforward than that of substances, whose toxicity in humans is wholly unexplored.
Elo
Hannu
H
Division of Pharmaceutical Biology, Faculty of Pharmacy, P.O. Box 56 (Viikinkaari 5, Biocenter 2), FIN-00014 University of Helsinki, Finland. Hannu.Elo@Helsinki.Fi
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013882:Thiosemicarbazones; C013996:2-formylpyridine thiosemicarbazone; D012264:Ribonucleotide Reductases