全球每年约有100万人死于疟疾，疟原虫耐药性的快速增强与研制新型抗疟药物的速度趋缓之间的矛盾日益尖锐，从海洋生物中寻找具有抗疟活性的结构新颖的药物先导化合物已成为抗疟药物研发的新思路。申请人以疟原虫Plasmodium falciparum筛选模型为指导，从采自西沙群岛的海绵Diacarnus megaspinorhabdosa和Aaptos aaptos中发现了两种结构新颖且具有强抗疟活性的系列化合物（环内过氧降萜类和aaptmine生物碱类）。本课题拟在此基础上，以活性导向结合化学官能团导向对该两种类型的化合物进行追踪分离，并对aaptamine系列中活性突出且含量较大的化合物利用Sandmeyer, Suzuki-Miyaura coupling, 氨基缩合等反应进行化学结构修饰和优化，以扩充其分子化学多样性，评价其体外和体内抗疟活性，初步探讨其作用机制，寻找出高效低毒的先导化合物。

Malaria is an infectious disease causing about 1 million deaths per year, the number of new drugs active against malaria continues to be very small comparing to the rapidly increasing of resistance. Searing for new bioactive chemical entities from secondary metabolites of marine organisms has become a new R&D direction of antimalarial drugs. Two novel skeletons with significant antimalarial activity have been found by bio-guided separation from two marine sponges Diacarnus megaspinorhabdosa and Aaptos aaptos collected from Paracel Islands. On this basis, the proposal focuses on the norditerpene endoperoxide and aaptamine derivatives by the combination of bio-guided and chemical functional group-guided separation. The in vitro and in vivo bioactivities and the mechanism of the compounds will be evaluated.In order to expend the chemical diversity to discover the high efficiency with low toxicity leads, the chemical modification and optimization of the aaptamine-type bioactive metabolites will also be made by utilizing Sandmayer, Suzuki-Miyaura coupling, and condensation reactions.