Synthesis of novel papulacandin D analogs and evaluation of their antifungal potential

Systemic fungal infections are a growing problem in contemporary medicine and few drugs are licensed for therapy of invasive fungal infections. Differences between fungi and humans, like the presence of a cell wall in fungal cells, can be explored for designing new drugs. (1,3)-β-D-glucan synthase, an enzyme that catalyzes the synthesis of (1,3)-β-D-glucan, a structural and essential component of the fungal cell wall, is absent in mammals and this makes it an excellent target for the development of new antifungal agents. Papulacandins are a family of natural antifungal agents targeting (1,3)-β-D-glucan synthase. In this study we describe the synthesis and biological evaluation of two new Papulacandin analogs as potential (1,3)-β-D-glucan synthase inhibitors.

全身性真菌感染在现代医学中已成为日益严峻的问题，获批用于治疗侵袭性真菌感染的药物寥寥无几。真菌与人类宿主之间的差异（例如真菌细胞具有细胞壁）可用于设计新型抗真菌药物。(1,3)-β-D-葡聚糖合酶（(1,3)-β-D-glucan synthase）是一种催化合成(1,3)-β-D-葡聚糖的酶，而(1,3)-β-D-葡聚糖是真菌细胞壁的结构必需组分；该酶在哺乳动物体内并不存在，因此成为开发新型抗真菌剂的绝佳靶点。帕普卡丁类（Papulacandins）是一类靶向(1,3)-β-D-葡聚糖合酶的天然抗真菌剂。本研究报道了两种新型帕普卡丁类类似物的合成，及其作为(1,3)-β-D-葡聚糖合酶潜在抑制剂的生物学评价。