Abstract
Methyl S (or 4) - (3,3 - dimethyl −1 - triazeno) imidazole-4 (or 5)-carboxylate(1), designated NSC 87982 by the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, has been reported to be a potent inhibitor of Gram-positive and Gram-negative bacteria, yeasts, filamentous fungi and algae in vitro and to protect mice against an experimental infection of Staphylococcus aureus (2). Microbiological assay of various mouse tissues indicates that not only are significantly high blood levels obtained following oral, intraperitoneal, or intravenous administration of the drug, but also that detectable concentrations of NSC 87982 are found in the brain and other organs of the mice(3). The broad-spectrum antimicrobial activity of NSC 87982 and the knowledge that it is being considered for clinical trial prompted a study of the mechanism of action of this compound.
Materials and methods. The inhibitory activity of NSC 87982 against numerous strains of Escherichia coli and Streptococcus faecalis which are resistant to various antimicrobial agents or radiation(4) was determined using previously described procedures (5); the spread-plate procedure(6) was used to determine the effect of metabolites (amino acids, B vitamins, purines, pyrimidines) on inhibition of E. coli by NSC 87982-details of this technique have been reported (7,8). Protein determinations were made by the method of Lowry et al (9). Ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) were determined by procedures previously described (10,11). By serial transfer in a simple glucose-salts medium containing increasing concentrations of NSC 87982, a culture of E. coli ATCC 9637 was obtained, (designated E. coli/NSC 87982) which is 30-foldresistant to the inhibitor.
Results and discussion. Strains of E. coli or S. faecalis resistant to various antibiotics, antimetabolites, or irradiation were not cross-resistant to NSC 87982.
Get full access to this article
View all access options for this article.