毛秔子梢中天然高活性的神经氨酸酶抑制成分的研究

Chemical Constituents with Neuraminidase Inhibitory Actives from Campylotropis Hirtella

从天然产物中筛选高效低毒的神经氨酸酶抑制剂（NAI），以期发现可抗流感病毒（H1N1）的化合物．方法：采用经典的NA活性检测实验（FL-MH-NANA method），对从豆科植物毛杭子梢中分离得到10个化合物进行筛选，检测这些化合物对NA的抑制活性．结论：化合物1，2，3，5对流感病毒株的神经氨酸酶（NA）均具有抑制作用，其中化合物1的抑制活性最强，其IC50值为16．76pmol／L．化合物1～4为新化合物，化合物5～10为该植物中首次分得．

Influenza is and remains a disease to reckon with. Seasonal epidemics around the world kill several hundred thousand people every year. Development of effective drugs for the treatment or prevention of epidemic and pandemic influ- enza is important in order to reduce its impact. Neuraminidase inhibitors is a class of anti-influenza drugs available for influ- enza therapy currently. However, emergence of resistance to these drugs has been detected, which raises concerns regarding their widespread use. Therefore, the search for low toxic natural neuraminidase inhibitor is one of the route for finding new anti-influenza virus drugs. In current study, the classical MUNANA-based NA activity assay was established to assess the neuraminidase inhibitory activities of compounds isolated from Campylotropis hirtella. The bioassay guided separation of 95% ethanol extract of the dried root of C. hirtella has led to the isolation of ten compounds, and their structures were eluci- dated on the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques. Compounds 1-4 are new compounds and these are two chromones, an isoflavone and a glycosides. Compounds 5-10 were isolated from C. hir- tella for the first time. All compounds were assesses for their inhibitory activities against influenza AI（H1N1） virus NA. Compounds 1, 2, 3, 5 showed good and dose dependent inhibitory effects against NA enzyme. Among them, compound 1 had the best NA inhibitory activity with the ICs0 at 16.76 pznol/L. Although, compound 1 is less active than Tamiflu, however, the results from the study demonstrated that isoflavone and chromone could be potent neuraminidase inhibitor. Since the struc- ture of compound 1 is very similar to Hirtellanine B, an isoflavonoid isolated from the same herb with potent antiproliferative effects in cancer cells, the biosynthetic pathway of both compound 1 and Hirtellanine B were proposed.