Evidence for the Mechanism of Action of the Antifungal Phytolaccoside B Isolated from Phytolacca tetramera Hauman

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2008-10, Vol.71 (10), p.1720-1725
• Main Authors: Escalante, Andrea, Gattuso, Martha, Pérez, Pilar, Zacchino, Susana
• Format: Article
• Language: English
• Subjects: Antifungal Agents - blood; Antifungal Agents - pharmacology; antifungal properties; Argentina; Aspergillus flavus; Aspergillus fumigatus; Aspergillus niger; Biological and medical sciences; Candida albicans; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell Wall - chemistry; chitin synthase; Cryptococcus neoformans; enzyme inhibition; General pharmacology; Glucosyltransferases - antagonists & inhibitors; glycosides; Glycosides - chemistry; Glycosides - isolation & purification; Glycosides - pharmacology; hemolysis; Humans; Medical sciences; Microscopy, Fluorescence; minimum inhibitory concentration; Neurospora crassa; oleanolic acid; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - blood; Oleanolic Acid - chemistry; Oleanolic Acid - isolation & purification; Oleanolic Acid - pharmacology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytolacca; Phytolacca - chemistry; Phytolacca tetramera; Phytolaccaceae; phytolaccoside; Plants, Medicinal - chemistry; Saccharomyces cerevisiae; Saccharomyces cerevisiae - chemistry; saponins; Saponins - blood; Saponins - chemistry; Saponins - isolation & purification; Saponins - pharmacology; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; triterpenoids; yeasts
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np070660i

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)-β-d-glucan synthase, an enzyme that catalyzes the synthesis of (1→3)-β-d-glucan, one of the major polymers of the fungal cell wall. However, enzymatic assays revealed that 1 did not inhibit (1→3)-β-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.