Evidence for the mechanism of action of the antifungal phytolaccoside B isolated from Phytolacca tetramera Hauman.
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.
Escalante
Andrea
A
Area Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Gattuso
Martha
M
Pérez
Pilar
P
Zacchino
Susana
S
D000935:Antifungal Agents / Q000097:blood / Q000494:pharmacology; D001118:Argentina; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029603:Phytolacca / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D012503:Saponins / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000935:Antifungal Agents; D006027:Glycosides; D012503:Saponins; D014315:Triterpenes; C421868:enfumafungin; C472597:phytolaccoside B; D009828:Oleanolic Acid; D005964:Glucosyltransferases; C040232:glucan synthase