epiglucan has been researched along with enfumafungin* in 3 studies
3 other study(ies) available for epiglucan and enfumafungin
| Article | Year |
|---|---|
MK-5204: An orally active β-1,3-glucan synthesis inhibitor.
Our previously reported efforts to produce an orally active β-1,3-glucan synthesis inhibitor through the semi-synthetic modification of enfumafungin focused on replacing the C2 acetoxy moiety with an aminotetrazole and the C3 glycoside with a N,N-dimethylaminoether moiety. This work details further optimization of the C2 heterocyclic substituent, which identified 3-carboxamide-1,2,4-triazole as a replacement for the aminotetrazole with comparable antifungal activity. Alkylation of either the carboxamidetriazole at C2 or the aminoether at C3 failed to significantly improve oral efficacy. However, replacement of the isopropyl alpha amino substituent with a t-butyl, improved oral exposure while maintaining antifungal activity. These two structural modifications produced MK-5204, which demonstrated broad spectrum activity against Candida species and robust oral efficacy in a murine model of disseminated Candidiasis without the N-dealkylation liability observed for the previous lead. Topics: Administration, Oral; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Disease Models, Animal; Glucosyltransferases; Glycosides; Half-Life; Mice; Microbial Sensitivity Tests; Stereoisomerism; Structure-Activity Relationship; Triazoles; Triterpenes | 2020 |
Novel orally active inhibitors of β-1,3-glucan synthesis derived from enfumafungin.
The clinical success of the echinocandins, which can only be administered parentally, has validated β-1,3-glucan synthase (GS) as an antifungal target. Semi-synthetic modification of enfumafungin, a triterpene glycoside natural product, was performed with the aim of producing a new class of orally active GS inhibitors. Replacement of the C2 acetoxy moiety with various heterocycles did not improve GS or antifungal potency. However, replacement of the C3 glycoside with an aminoether moiety dramatically improved oral pharmacokinetic (PK) properties while maintaining GS and antifungal potency. Installing an aminotetrazole at C2 in conjunction with an N-alkylated aminoether at C3 produced derivatives with significantly improved GS and antifungal potency that exhibited robust oral efficacy in a murine model of disseminated candidiasis. Topics: Administration, Oral; Animals; Antifungal Agents; Aspergillus fumigatus; beta-Glucans; Candida albicans; Candidiasis; Glucosyltransferases; Glycosides; Half-Life; Mice; Microbial Sensitivity Tests; Structure-Activity Relationship; Terpenes; Triterpenes | 2015 |
The composition of the culture medium influences the β-1,3-glucan metabolism of Aspergillus fumigatus and the antifungal activity of inhibitors of β-1,3-glucan synthesis.
In vitro testing of Aspergillus fumigatus susceptibility to echinocandins has always been a challenge. Using a simple and quick colorimetric method to analyze the activity of inhibitors of β-1,3-glucan synthesis, we found that the composition of the culture medium significantly influences glucan synthesis and consequently the antifungal properties of inhibitors of β-1,3-glucan synthesis when they are tested alone or in combination with chitin synthase inhibitors. Topics: Antifungal Agents; Aspergillus fumigatus; beta-Glucans; Caspofungin; Culture Media; Echinocandins; Glycosides; Lipopeptides; Miconazole; Microbial Sensitivity Tests; Triterpenes | 2012 |