癌症严重威胁着人类的健康和生存，已经成为中国的第一大死亡病因。由于化疗药物的持续使用，癌细胞的多药耐药性被认为是一个重大的挑战。因此，急需研发新型有效的抗肿瘤药物。海洋天然产物因其化学结构新颖、药理活性显著，已经成为开发新型药物的重要资源。前期研究中，从一株软珊瑚来源的真菌Aspergillus sp.中发现了2个具有显著细胞毒活性的新颖生物碱aspergilimides A和B（1和2）。该类结构中含有特殊氨基酸残基的喹唑啉稠酰亚胺结构骨架。在已有工作基础上，本项目拟在分子网络技术指导下进一步开展该类新颖生物碱化合物的多样性研究，并进行细胞毒活性和基于斑马鱼的抗肝癌活性筛选评价及初步构效关系研究，以期发现具有潜在开发价值的活性化合物，为新型抗肿瘤药物研究提供化合物基础。

Cancer is a major public health problem worldwide and is the first leading cause of death in China. With the continued using of chemotherapy drugs, multidrug resistance in cancer cells is considered a major challenge. Therefore, screening new compounds for the treatment of cancer remain an unmet medical need. Marine natural products have been proven to be rich sources of structurally novel and biologically active compounds, and they have become one of the major chemical entities for drug discovery. Recently, two quinazoline-ketopiperazine alkaloids (1 and 2) with unprecedented amino acid residue were isolated from the gorgonian-derived fungus Aspergillus sp. Compounds 1 and 2 showed strong cytotoxicity against tumor cell lines K562. This project will deeply explore the novelty and structural diversity of alkaloids from this fungus under the guidance of molecular networking, and evaluate their in vitro cytotoxicity, in vivo inhibitory activity against live tumorigenesis and anti-angiogenic effect using transgenic zebrafish. This project will provide an important basis for the development of new marine-derived antitumor lead compounds.