疟疾迄今仍是公众健康所面临的严重威胁之一，而耐药恶性疟的泛滥使该形势愈加严峻。云南隶属大湄公河疟疾流行区域，是全国耐药恶性疟滋生和蔓延的高危地带。围绕云南耐药恶性疟问题，项目组针对傣药决明属中特有的抗疟活性生物碱开展了前期研究：运用化学生物联合筛选方法，精选出生物碱种类丰富且活性显著的双荚决明和长穗决明；并初步从双荚决明中发现了多个具有较强抑制云南境内耐药恶性疟的新颖异喹啉生物碱（包括4种新的类型）。基于以上重要发现，本项目拟从三个方面开展系统研究：进一步对两种决明中的特有生物碱开展跟踪分离；分离得到的生物碱开展四种滇境内恶性疟原虫的体外活性筛选和初步的构效关系探讨；富集活性显著的生物碱并开展体内抗疟活性测试。该项目的主要目的是运用植物化学、化学转化、生物活性筛选等方法来发现具有抗耐药疟原虫的先导化合物，其成功实施可能为预防我国西南地区耐药恶性疟泛滥以及研发新型抗疟药物提供有益的探索。

To date, malaria remains one of the most dangerous diseases in the world, and the spread of Plasmodium falciparum drug resistance makes this situation even worse. Yunnan province, which belongs to the Greater Mekong Subregion (GMS), is the most threatening foci of the emergence and rapid widespread of P. falciparum drug resistance in China. Aiming at the issue of drug-resistant falciparum malaria in Yunnan province, we have performed previous studies on the antiplasmodial alkaloids from the genus of Cassia used in the Chinese Dai tribal folk medicine. Firstly, we selected the alkaloids extracts of C. bicapsularis and C. didymobotrya with potential diverse structures and biological properties using a screening phase for the chemical diversity combined with biological activity. Furthermore, the preliminarily phytochemical investigation on the C. bicapsularis led to the discovery of many new isoquinoline alkaloids (including four novel types) with significant antimalarial activity against drug-resistant malaria strain in Yunnan province. Based on these new results, we will initiate this program in three aspects: investigating on the chemical constituents of C. bicapsularis and C. didymobotrya; screening the in vitro antimalarial activity of the isolated isoquinoline alkaloids against four malaria strains from Yunnan province, and discussing their structure-activity relationship; enriching enough bioactive alkaloids and testing in vivo antiplasmodial activity. The main purpose of this program is performed to discover antiplasmodial lead compounds by the combined strategy of phytochemistry, chemical conversion, biological research, and so on. This research may provide a useful exploration for preventing the spread of P. falciparum drug resistance in southwest China and developing the innovative antimalarial agents.