新型N-取代邻苯二甲酰亚胺类衍生物抗肿瘤血管生成活性评价

目的 对前期合成的邻苯二甲酰亚胺衍生物的抗肿瘤血管生成活性进行评价.方法 应用体外细胞培养模型、体内斑马鱼模型和C57BL/6荷瘤小鼠模型对化合物的抗肿瘤血管生成活性进行考察.结果 N-苄基-4,6-二甲氧基邻苯二甲酰亚胺(7i)和N-苄基-4,6-二-羟基邻苯二甲酰亚胺(8i)能够显著抑制人肺腺癌A549细胞中血管内皮生长因子分泌,同时能够抑制斑马鱼体节间血管生成.两种化合物抑制Lewis肺腺癌移植瘤生长,并优于阳性对照药沙利度胺.结论 所合成的新型邻苯二甲酰亚胺类衍生物具有一定的抗肿瘤血管生成作用,具有进一步合成修饰研究价值.

Antitumor angiogenic activities of novel phthalimide derivatives

Objective To evaluate the antitumor angiogenic activities of the phthalimide derivatives.Methods Cell culture model in vitro,zebrafish embryos and tumor-burdened mice model in vivo were used to evaluate the antitumor angiogenic activities.Results The secretion of VEGF in A549 cells was significantly decreased by compounds N-benzyl-4,6-dimethoxy-isoindoline-1,3-dione(7i) and N-benzyl-4,6-dihydroxyy-isoindoline-1,3-dione (8i).Moreover,the formation of intersegmental vessels (ISVs) in zebrafish embryo model was also inhibited by these two compounds. Furthermore,solid melanoma grown in right oxter of mice was obviously inhibited.Conclusion The antitumor angiogenic activity of synthesized phthalimide derivatives had research value for further synthesis modification.