马铃薯三糖五环三萜类化合物体外抗H5N1流感病毒的活性评价

摘要

Aim To study the inhibitory activities of potential new anti-influenza virus agents,3-O-β-chaco-triosyl pentacyclic triterpenoids against the entry of H5N1influenza viruses.Methods Three target com-pounds were designed and synthesized structurally re-lated to the lead compound 3-O-β-chacotriosyl dioscin derivative (1 )with inhibitory activities against H5N1 influenza viruses.The inhibitory activities of these tar-get compounds were tested at a cellular level pseudo vi-rus system targeting H5N1 influenza viruse entry.Re-sults All the compounds 1 a,1 b and 1 c showed po-tent inhibitory activities against the entry of A/Thai-land/Kan353/2004 pseudo virus into the target cells, of which compound 1 b showed the best inhibitory activ-ity with an IC50 value of (1.25 ±0.22)μmol·L-1. Conclusion The SARs analysis of these compounds indicated that replacement of the aglycone moiety of compound 1 with pentacyclic triterpenoids could in-crease antiviral activity.Different types of pentacyclic triterpen as aglycone residue had the significant influ-ence on the inhibitory activity (1 b >1 c >1 a),sug-gesting ursane type of triterpenes was superior to the two other kinds of triterpenes as aglycone residue.%目的：研究3种不同类型的马铃薯三糖五环三萜能否通过抑制H5 N 1流感病毒进入靶细胞，作为潜在的新型抗流感药物进行研发。方法以马铃薯三糖薯蓣皂苷衍生物1为先导化合物，设计并合成3个目标化合物，利用建立的H5 N 1假病毒活性检测方法，测试化合物的抑制活性。结果目标化合物1 a、1 b和1 c对源自A／Thailand／Kan353／2004的H5N1假病毒毒株均具有明显的抑制作用，且化合物1b的活性最好，其IC50达到（1.25±0.22）μmol·L－1。结论初步构效关系研究表明，将先导化合物1结构中的薯蓣皂苷苷元替换成五环三萜苷元后可提高其抗病毒活性；五环三萜的苷元类型对抗病毒活性有重要影响，乌苏烷型的五环三萜为苷元其抗病毒活性最强。