厌氧病原菌是引发人类口腔疾病的罪魁祸首，其耐药性不断增强，因此发现新先导化合物、研发新型抗厌氧菌药物已成为临床用药的迫切需求。Curvularia sp. IFB-Z10是来自于海洋白姑鱼肠道的共生真菌，其产生的生物碱curvulamine对临床口腔厌氧菌具有显著抑制活性。为发现更多具有抗厌氧菌活性生物碱二聚体，本项目拟基于HPLC-DAD-MS技术优化培养基配方和培养条件，诱导Curvularia sp. IFB-Z10产生结构多样的生物碱二聚体；利用凝胶柱色谱、半制备型HPLC等仪器设计一条生物碱类二聚体的特异性富集和分离方法；综合利用现代波谱技术、X-射线单晶衍射技术等方法确定新化合物的平面结构和绝对构型；对分离的生物碱二聚体进行抗厌氧菌活性筛选、构效关系分析和活性机制研究。本项目致力于发现结构新颖、抗厌氧菌活性显著的新生物碱二聚体，为创新型海洋抗厌氧菌药物的研发提供先导化合物。

Anaerobic pathogens are the culprits of human oral diseases with the growing problem of antibiotic resistance. Thus, the search for new anti-anaerobic drugs had become an urgent need for patients. Curvularia sp. IFB-Z10 resided in the gut of white croaker (Argyrosomus argentatus). Curvulamine possessed novel dimeric alkaloid structure, and showed significant activity against clinical oral anaerobic bacteria with the MIC values from 0.32 to 0.77 μM. To find more anti-anaerobic agents, in this proposal, we focus on optimization of cultivation medium ingredients in order to producing alkaloid polymeric compounds using the HPLC-DAD-MS method; A specific targeted isolated method was designed for finding, identifying and separating alkaloid polymers with the help of sephadex LH-20 column chromatograph and pre-HPLC; Structures of isolated compounds and absolute configurations will be established by comprehensive modern spectroscopic techniques, single crystal X-ray diffraction methods etc. Anti-anaerobic activities of isolates will be screened, and their active mechanism will be studied. In this proposal, we look forward to finding novel structural dimmeric alkaloids with antimicrobial activities, which would provide lead compounds for new innovative drug research & development.