蒽吡唑类衍生物的合成及构效关系

Synthesis and structure activity relationship of anthrapyrazoles derivatives

目的以蒽醌为原料,与脂肪胺通过缩合反应合成系列蒽醌-胺基衍生物。方法利用1H NMR、MS、元素分析等方法对所合成的目标化合物进行了结构确认。结果肿瘤细胞生长抑制实验结果表明,该类蒽吡唑衍生物在相应的细胞模型显示出一定的肿瘤细胞生长抑制能力。利用髙亚精胺修饰的蒽醌衍生物对所测试细胞具有显著的生长抑制活性。结论初步的构效关系分析发现,蒽吡唑母核C-3位的化学修饰对提高蒽咇唑衍生物的抗肿瘤活性影响不大,然而侧链取代基对于改善其抗肿瘤作用具有显著影响。特别是利用多胺链修饰得到的衍生物不但能够有效提高抗肿瘤作用,还对耐药细胞SMMC-7721(耐药人肝癌细胞)表现较强的生长抑制作用。

Objective Several anthrapyrazoles derivatives were synthesized using anthraquinone and aliphatic amines as starting material.Methods The structure of the target compounds were confirmed by 1H NMR,MS and elemental analysis assays.Results The biological results indicated that these derivatives exhibited potent in vitro cytotoxicity against different cancer cell lines.Among them,the polyamine based anthrapyrazole derivatives showed superior cytotoxicity than that of Mitoxantrone both on cancer cell lines and the drug resistant subline.ConclusionThe structure activity relationship of these anthrapyrazoles derivatives demonstrated that the polyamine side chain could be helpful in improving the antitumor activity,while the C3 site on anthrapyzole had little effect on the cytotoxicity.