【摘要】 目的寻找高效低毒的9-硝基喜树碱类抗肿瘤新化合物。方法设计合成了7个9-硝基喜树碱季氨盐类衍生物,经1H-NMR,IR,MS分析确证化合物的结构,利用MTT法考察了这些化合物的体外抑制肿瘤细胞活性,并通过分子生物学方法评价了这些化合物的拓扑异构酶Ⅰ抑制活性。结果7个化合物的体外细胞毒活性都低于喜树碱和topotecan,其中化合物7,9,11的细胞毒活性与氟尿嘧啶相似。化合物7,9,10,12显示了较好的拓扑异构酶Ⅰ抑制活性。结论该类水溶的9-硝基喜树碱衍生物的抗肿瘤活性值得进一步研究。更多还原

【Abstract】 OBJECTIVE To find new anticancer compounds with high anticancer activity and low toxicity based on the structure of 9-nitrocamptothecin.METHODS Seven water soluble quaternary ammonium salt derivatives of 9-nitrocamptothecin were synthesized.The in vitro cytotoxicity of these derivatives was evaluated by MTT assay.And their inhibitory properties of topoisomeraseⅠwere determined by topoisomeraseⅠ-mediated DNA relax assay.RESULTS All of these salts showed lower cytotoxicity than camptothecin and topotecan.The compound 7,9,11 showed similar cytotoxic activity as 5-FU,and compound 7,9,10,12 had stronger inhibit acitivity to topoisomeraseⅠthan others analogues,but lower than camptothecin.CONCLUSION These water soluble derivatives of 9-nitrocamptothecin are worth further being developed.更多还原