苔藓植物中化合物结构多样性制备和抗真菌毒力研究

真菌感染发病普遍，真菌毒力伴随于真菌感染的过程，真菌毒力因子（VF）的表达与真菌对宿主的侵袭、感染、器官组织破坏等密切相关，VF具有病原特异性，因此以VF为靶点发现的抗真菌药，干预真菌的感染过程、更加符合临床实际。针对天然化合物结构多样性来源局限、化合物活性发现不足的问题，在对苔藓植物抗真菌活性成分研究的基础上，本课题利用化学工程/光化学法实现苔藓植物中天然化合物的结构多样性制备；以与真菌粘附、菌丝形成、侵袭、耐药等真菌感染环节密切相关的VF为靶点，建立高通量多维度筛选方法，筛选获得多样结构化合物，发现VF抑制剂；体内评价抗真菌活性，探讨抑制真菌毒力在抗真菌方面的意义和应用，为发现新型抗真菌药物奠定研究基础。

Fungal infection is one of the most common hospital-aquired infections. Virulence factors (VFs) are attributes of pathogens needed for infection. Targeting the virulence factors has been proposed as a new paradigm for antifungal drug discovery. As the VFs are usually pathogen-specific, VF inhibitor will have less side effects and more clinical significance by interfering the link between fungi and host. Our previous have found many VF inhibitory active compounds which are exclusive occurred in bryophytes. Our present investigation is to establish the screening methods based on the VF-targeting related to the formation of hyphae, biofilm, drug resistance in the invasion process; to diversify the bryophyte-derived natural compounds by chemical engineering or photo-driven chemical conversion; to high throughput screen of the compound library in multiways; to find the active VF inhibitors. In vitro and in vivo test of the active hits will provide antifungal leads for further investigation and will definitely provide one new way to fight fungal infection.