ABSTRACT
The preparation and antifungal properties of 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate 1 are described. It is particularly effective against in vivo Candida albicans infections (mice), maintaining good activity down to 0.25% formulation strength and showing unusually low reinfection rates after treatment is ended.
Subject(s)
Antifungal Agents/chemical synthesis , Imidazoles/chemical synthesis , Animals , Antifungal Agents/therapeutic use , Antifungal Agents/toxicity , Candida albicans/drug effects , Candidiasis, Vulvovaginal/drug therapy , Chlorobenzenes/chemical synthesis , Chlorobenzenes/pharmacology , Chlorobenzenes/therapeutic use , Chlorobenzenes/toxicity , Female , Imidazoles/pharmacology , Imidazoles/therapeutic use , Imidazoles/toxicity , Lethal Dose 50 , Mice , Microbial Sensitivity Tests , Microsporum/drug effects , Mutagens/chemical synthesis , Saccharomyces cerevisiae/drug effects , Salmonella typhimurium/drug effects , Trichophyton/drug effectsABSTRACT
The enterotoxic component in sterile syncase broth filtrates of Escherichia coli strains 340 (O9:K.:NM) and P307 (O8:K87,88a,b:H19) was studied. The enterotoxic activity in both strains was retained by an ultrafiltration membrane with a molecular weight retention of 100,000 (XM-100A) and eluted from a Sephadex G-200 column in the void volume. The enterotoxic activity in strain 340 was resistant to heating at 75 C for 30 min, but the activity in strain P307 was destroyed by heating at 60 C for 30 min. The P307 Sephadex G-200 column eluate possessing the enterotoxic activity, when desalted, contained 45.8% carbohydrate and 9.3% protein, and had an ED(50) of 2.2 mg/rabbit ileal loop. Immunodiffusion studies showed that this material contained both endotoxin and acid-polysaccharide capsular material. The enterotoxic activity was acidlabile and was destroyed by Pronase, but was resistant to trypsin and eluted as a single peak in the void volume of a 4% agarose column. The enterotoxic component could not be separated from the endotoxin; in fact, the data indicated that the two components are closely associated and that the enterotoxic activity resides in material of a protein nature.
