紫铆素类衍生物的合成及其体外免疫活性的评价

Synthesis and immunoregulation of butin derivatives

目的以紫铆素为母核合成20个化合物(1～20),并进行体外免疫活性的评价,为临床上寻找新型免疫调节剂提供实验依据。方法以紫铆素为母核,在3'和4'位引入不同基团合成一系列衍生物(1～20),MTT法检测目标化合物对刀豆蛋白(Con A)刺激的小鼠脾淋巴细胞增殖率的影响,ELISA试剂盒检测化合物对小鼠脾淋巴细胞上清中免疫相关因子IL-4、Ig-G、TNF-α分泌情况的影响。结果化合物1、2、3、4、5、15、16、17、18、19、20可以显著抑制ConA对小鼠脾淋巴细胞的增殖反应,同时化合物3、4可以显著抑制IL-4的分泌,化合物1、3、17可以抑制TNF-α的分泌,4、5和20则可以显著促进IgG的分泌。结论化合物1、3、4、17对小鼠脾淋巴细胞的免疫功能具有抑制作用,这些衍生物有可能成为潜在的免疫抑制剂。

Objective To synthesize a series of derivatives,evaluate their immunoregulation in vitro,and provide theoretical basis for clinical immune modulators.Methods We synthesized a series of derivatives（1-20） with butin as the parent nucleus.The influence of molecular derivatives on ConA-induced lymphocytes was detected by MTT assay.Cytokines TNF-α,IL-4,and IgG of the lymphocytes were detected with ELISA to determine the optimal concentration to observe the influence of immunoregulation.Results In vitro test showed the derivatives 1,2,3,4,5,15,16,17,18,19 and 20 at 1 μmol L-1 inhibited ConA-induced splenocyte proliferation,and derivatives 3 and 4 significantly inhibited the secretion of IL-4.Derivatives 4,5 and 20 at 1 μmol L-1 strengthened the secretion of IgG.Conclusion The derivatives（1,3,4 and 17） may become potential immunomodulators for mice.