瑞香素结构衍生物体内外抗疟活性的研究  

The potentiation of antimalarial activities by daphnetin derivatives against malaria parasites in vitro and in vivo

作　　者：黄芳[1] 汤林华[1] 余琳千[2] 倪奕昌[1] 王琴美[1] 周水森[1] 

机构地区：[1]中国疾病预防控制中心寄生虫病预防控制所,世界卫生组织疟疾、血吸虫病和丝虫病合作中心,上海200025 [2]中国科学院药物所,国家新药筛选中心,上海200025

出　　处：《中国病原生物学杂志》2008年第1期35-38,共4页Journal of Pathogen Biology

摘　　要：目的通过体外试验和鼠疟(Plamodium berghei)动物模型观察瑞香素结构衍生物的抗疟作用。方法通过光学显微镜镜检和微量荧光法两种体外筛选系统筛检瑞香素类衍生物对恶性疟原虫(Plamodium falciparum)的体外抗疟作用;对体外筛检抗疟活性高的化合物,采用WHO推荐的"四天抑制试验"测定其对鼠伯氏疟原虫(ANKA株)的抗疟作用。结果通过体外筛选系统筛选出DA78与DA79两种新型的瑞香素类抗疟化合物,两者的IC50分别为7.6μmol/L和1.4μmol/L,其体外抗疟活性与瑞香素在同一统计学水平(P>0.05);体内试验伯氏鼠疟原虫ANKA株感染鼠,DA78 1、10、50、75 mg/kg.d×4 d剂量组D4减虫率与空白对照组比较差异有显著性(P<0.01),而DA79 50或75 mg/kg.d×4 d剂量组D4减虫率与对照组相比较差异有显著性(P<0.05),DA78 10或75 mg/kg.d×4 d剂量组D4减虫率高于同剂量的瑞香素组(P<0.05)。结论以DA78与DA79为代表的瑞香素类衍生物作为一类新型的抗疟化合物,在体外和体内试验中均显示出一定的抗疟活性,为寻求更有效的抗疟化合物提供了方向和理论依据。Objective To screen antimalarial activities of daphnetin derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Methods The antimalarial activities of daphnetin derivatives against P. falciparum in vitro were screened by microscopy-based assay and microfluorimetric method. The schizontocidal effect of daphnetin derivatives with potent antimalarial activity in vivo assay were tested in mice infected with P. beighei ANKA according to the ＂4-day suppress assay＂ recommended by WHO. Results DA78 and DA79 showed potent antimalarial activities against P. falciparum in vitro at the same level of daphnetin. The ICso values of DA78 and DA79 were 7.6μmol/L and 1.4 μmol/L, respectively. The in vivo antimalarial effects of DA78 and DA79 was assessed by reduction rate of parasitemia on day 4. The reduction rate of parasitemia on D4 treated with 1,10,50,75 mg/kg·d×4 d DA79 intragastrically whereas control group had significant difference （P〈0.01）, and the reduction rate of parasitemia on D4 treated with 50 or 75 mg/kg· d×4 d DA78 intragastrically whereas control group had significant difference （P〈0.05）. The antimalarial efficacy of DA79 10 or 75 mg/kg·d×4 d were better than the same dosage of daphnetin. Conclusion As new antimalarial compounds, daphnetin derivatives DA78 and DA79 Showed antimalarial activity in vitro and in vivo, which might provide a new direction to discovery of more effective antimalarial compounds and have laid a basis for further research and development of daphnetin derivatives antimalarial drugs.

关 键 词：瑞香素 抗疟药物 筛选 伯氏疟原虫 恶性疟原虫 

分 类 号：R382.31[医药卫生—医学寄生虫学]