1. Evidence for the mechanism of action of the antifungal phytolaccoside B isolated from Phytolacca tetramera Hauman.
- Author
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Escalante A, Gattuso M, Pérez P, and Zacchino S
- Subjects
- Antifungal Agents blood, Antifungal Agents pharmacology, Argentina, Cell Membrane chemistry, Cell Membrane metabolism, Cell Wall chemistry, Glycosides chemistry, Glycosides isolation & purification, Glycosides pharmacology, Humans, Microscopy, Fluorescence, Oleanolic Acid blood, Oleanolic Acid chemistry, Oleanolic Acid isolation & purification, Oleanolic Acid pharmacology, Saccharomyces cerevisiae chemistry, Saponins blood, Saponins chemistry, Triterpenes chemistry, Triterpenes isolation & purification, Triterpenes pharmacology, Glucosyltransferases antagonists & inhibitors, Oleanolic Acid analogs & derivatives, Phytolacca chemistry, Plants, Medicinal chemistry, Saponins isolation & purification, Saponins pharmacology
- Abstract
Phytolaccoside B (1), an antifungal monodesmoside triterpenoid glycoside isolated from berries of Phytolacca tetramera Hauman (Phytolaccaceae), alters the morphology of yeasts and molds. The malformations were similar to those produced by enfumafungin, a known inhibitor of (1-->3)-beta-D-glucan synthase, an enzyme that catalyzes the synthesis of (1-->3)-beta-D-glucan, one of the major polymers of the fungal cell wall. However, enzymatic assays revealed that 1 did not inhibit (1-->3)-beta-D-glucan synthase, but it did produce a notable enhancement of the chitin synthase 1 activity and, concomitantly, a rise in chitin, another important polymer of the fungal cell walls. This finding was corroborated by fluorescence microscopy and also by quantification of the chitin. In addition, a 2-fold increase in the thickness of the fungal cell wall was observed with transmission electronic microscopy. On the other hand, 1 neither bound to ergosterol nor caused hemolysis of red blood cells, although some fungal membrane damage was observed at the MIC of 1.
- Published
- 2008
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