r-120758 and Candidiasis

r-120758 has been researched along with Candidiasis* in 3 studies

Other Studies

3 other study(ies) available for r-120758 and Candidiasis

ArticleYear
Design, synthesis and antifungal activity of the novel water-soluble prodrug of antifungal triazole CS-758.
    Chemical & pharmaceutical bulletin, 2010, Volume: 58, Issue:6

    CS-758 was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, phosphoryl ester prodrugs were designed. In this study, the synthesis and evaluation of these injectable prodrugs are described. Phosphoryl ester 17 h was soluble in water, and was stable in both water and in a solid state. 17 h was converted to CS-758 in human liver microsome and was also converted to CS-758 in rats after intravenous (i.v.) administration with good conversion speed and efficiency. 17 h (i.v.) reduced the viable cell counts in kidneys in a murine hematogenous Candida albicans infection model and in lungs in a murine pulmonary Aspergillus fumigatus infection model, wherein the effects were comparable to or slightly superior to that of CS-758 (per os).

    Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Humans; Mice; Microsomes, Liver; Mycoses; Prodrugs; Rats; Solubility; Triazoles

2010
Synthesis, cleavage, and antifungal activity of a number of novel, water-soluble ester prodrugs of antifungal triazole CS-758.
    Bioorganic & medicinal chemistry letters, 2009, Jul-01, Volume: 19, Issue:13

    In this study, the synthesis and evaluation of a number of esters of CS-758 as injectable prodrugs are described. Phosphoryl ester 1a was soluble in water (>30mg/mL) and was converted to CS-758 in human liver microsome. It was also converted to CS-758 in rats after iv administration, wherein the bioavailability of CS-758 was 53%. Compound 1a (iv) reduced the viable cell counts in kidneys in a murine systemic Candida albicans infection model, wherein the effect was comparable to or slightly superior to that of CS-758 (po). The prodrug 1a proved to be a promising injectable antifungal agent whose further evaluation is warranted.

    Topics: Animals; Antifungal Agents; Candidiasis; Humans; Mice; Microsomes, Liver; Prodrugs; Rats; Triazoles; Water

2009
Efficacy of CS-758, a novel triazole, against experimental fluconazole-resistant oropharyngeal candidiasis in mice.
    Antimicrobial agents and chemotherapy, 2003, Volume: 47, Issue:2

    The therapeutic efficacy of CS-758, a novel triazole, was evaluated against experimental murine oropharyngeal candidiasis induced by Candida albicans with various susceptibilities to fluconazole. Against infections induced by strains with various susceptibilities to fluconazole, the efficacy of fluconazole was strongly correlated with the MIC of fluconazole, as measured by the NCCLS method, and agreed with the NCCLS interpretive breakpoints, suggesting that the efficacies of new drugs could be predicted by using this model. The results of the fungal burden study corresponded with the results of the histopathological study. CS-758 exhibited potent in vitro activity (MICs, 0.004 to 0.06 micro g/ml) against the strains used in this murine model including fluconazole-susceptible dose-dependent and fluconazole-resistant strains (fluconazole MICs, 16 to 64 micro g/ml). CS-758 exhibited excellent efficacy against the infections induced by all the strains including a fluconazole-resistant strain, and the reductions in viable cell counts were significant at 10 and 50 mg/kg of body weight/dose. Fluconazole was not effective even at 50 mg/kg/dose against infections induced by a fluconazole-resistant strain (fluconazole MIC, 64 micro g/ml). These results suggest that CS-758 is a promising compound for the treatment of oropharyngeal candidiasis including fluconazole-refractory infections.

    Topics: Animals; Antifungal Agents; Candidiasis; Drug Resistance, Fungal; Fluconazole; Male; Mice; Microbial Sensitivity Tests; Oropharynx; Tongue; Triazoles

2003