Research of the antimalarial drugs from the natural products

我们一直在研究从天然产物中发现新型抗疟疾药物。在4年的研究期间，共有12832份样品作为天然产物提供给北内筛选中心进行体外抗疟筛查。因此，我们选择的候选材料为18种具有选择性和有效抗疟活性的天然产物，这些候选材料必须进一步检测从这些材料中分离和纯化活性化合物。在微生物代谢产物的研究过程中，我们发现放线菌菌株K99-0413、KP-4050、K99-5147、KP-4093（后被选为高产菌株OM-0060）和真菌菌株FKI-0266分别产生的5种已知抗生素（X-206、K-41、聚酮霉素、borrelidin和leucinostatin A）在体外具有强效和选择性的抗疟活性。此外，我们发现高卡霉素（与贺霉素鉴定）和八环霉素是我们研究所抗生素文库中自己的化合物，在体外具有很强的活性。X-206、K-41和borrelidin的体内抗疟活性高于现有的蒿甲醚、青蒿琥酯和氯喹等抗疟药物。特别是K-41和borrelidin具有作为新型抗疟药物先导化合物的可能性，对K-41和borrelidin的进一步详细研究正在进行中。在对植物资源的研究过程中，我们从紫荆根中分离到两种已知的生物类黄酮，即sikokianins B和C，在体外具有中等的抗疟活性。上述化合物具有抗疟活性的报道尚属首次。现在，我们正在测量其他天然化合物的抗疟疾活性，如海洋产品和从天然产品中提取的合成化合物，并正在从其他天然产品中分离活性物质。

We had researched to discover new type of the antimalarial drugs from the natural products. During the research period of 4 years, 12, 832 samples as the natural products were supplied to the Kitasato screening center for in vitro antimalarial screening. As a result, we selected the candidate materials as 18 natural products that had selective and potent antimalarial activities, which must be examined further isolation and purification of active compounds from those materials. In the course of the research from the microbial metabolites, we found that the five known antibiotics (X-206, K-41, polyketomycin, borrelidin and leucinostatin A) produced by actinomycete strains K99-0413, KP-4050, K99-5147, KP-4093 (later, OM-0060 was selected as highly productive strain) and a fungal strain FKI-0266, respectively, had potent and selective antimalarial activities in vitro. Further, we found that takaokamycin (identified with hormomycin) and octacyclomycin, own compounds in the antibiotic library of our institute, had potent activity in vitro. Furthermore, the in vivo antimalarial activities of X-206, K-41 and borrelidin exhibited more potent activities than those of the existed antimalarial drugs as artemether, artesunate and chloroquine. Especially, K-41 and borrelidin has the possibility of the lead compounds as the new type of the antimalarial drugs, further detail studies of K-41 and borrelidin are in progress. In the course of the research from the plant resources, we found that two known biflavonoids as sikokianins B and C were isolated from the root of Wikstroemia indica, had moderate antimaralial activities in vitro. There are the first reports to show antimalarial activities of the above compounds. Now, we are ongoing to measure the antimalarial activities of other natural compounds as marine products and synthetic compounds derived from the natural products, and also ongoing to isolate active substances from the other natural products.