Evidence for the Mechanism of Action of the Antifungal Phytolaccoside B Isolated from Phytolacca tetramera Hauman
Evidence for the Mechanism of Action of the Antifungal Phytolaccoside B Isolated from Phytolacca tetramera Hauman
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DOI：
10.1021/np070660i
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发表时间：
2008-10-01
影响因子：
5.1
通讯作者：
Zacchino, Susana
中科院分区：
文献类型：
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作者：
Escalante, Andrea;Gattuso, Martha;Zacchino, Susana
商陆苷B（1）是从商陆科商陆属植物Phytolacca tetramera Hauman的浆果中分离得到的一种抗真菌的单桥糖苷三萜类糖苷，可改变酵母菌和霉菌的形态。这些畸形与恩夫马芬净产生的畸形相似，恩夫马芬净是一种已知的（1 -> 3）-β-D-葡聚糖合酶抑制剂，（1 -> 3）-β-葡聚糖合酶是一种催化（1 -> 3）-β-葡聚糖合成的酶，是真菌细胞壁的主要聚合物之一。然而，酶测定显示1不抑制（1 -> 3）-β-D-葡聚糖合酶，但它确实产生几丁质合酶1活性的显著增强，并且伴随着几丁质（真菌细胞壁的另一种重要聚合物）的增加。这一发现证实了荧光显微镜和定量的几丁质。此外，用透射电子显微镜观察到真菌细胞壁的厚度增加了2倍。另一方面，I既不与麦角固醇结合也不引起红细胞溶血，尽管在MIC为1时观察到一些真菌膜损伤。
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-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, I neither bound to ergosterol nor caused hemolysis of red blood cells, although some fungal membrane damage was observed at the MIC of 1.