抗肿瘤鬼臼毒素类衍生物的合成

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1、授予单位代码10089_学号或申请号11203对处(E搿大奁HebeiMedicalUniversity硕士学位论文在职科学学位抗肿瘤鬼白毒素类衍生物的合成学位申请人：郝鹤导师：陈虹教授专业：药理学二级学院：武警后勤学院2015年3月河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师（或指导小组）的指导下，由本人独立完成。本学位论文研究所获得的研究成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公开和使用。凡发表与学位论文主要内容相关的论文，第一署名为单位河北医科大学，试验材料、原始数据、

2、申报的专利等知识产权均归河北医科大学所有。否则，承担相应法律责任。研究生签名：奇f难€导师签章：二级学院领导盖章:(y年4月>曰河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研究工作及取得的研究成果，除了文中特别加以标注和致谢等内容外，文中不包含其他人已经发表或撰写的研究成果，指导教师对此进行了审定。木论文由本人独立撰写，文责自负。研究生签名：品师签n下、K年〈月y日目录中文摘要···································································

3、···········1英文摘要··············································································4英文缩写··············································································8研究论文抗肿瘤鬼臼毒素类衍生物的合成前言····································································

4、··········9材料与方法····································································10结果·············································································13附图·············································································22讨论················

5、·····························································34结论·············································································35参考文献·······································································35综述抗肿瘤药鬼臼毒素及其衍生物的研究进展·························

6、···36致谢···················································································45个人简历·············································································46中文摘要抗肿瘤鬼臼毒素类衍生物的合成摘要肿瘤严重威胁着人类的健康和生命。目前，化学治疗是目前临床治疗肿瘤的主要治疗方法之一。肿瘤化疗药物的研究与开发已取得了很大的进展，肿瘤患者的生存

7、期明显延长，治愈率也显著提高。然而，化疗也存在许多问题，如毒性大，治疗窗窄，尤其是越来越严重的肿瘤多药耐药性，后者(MDR)是导致肿瘤化疗失败的重要原因，是肿瘤化疗急需解决的一大难题。因此寻找高效、低毒、抗多药耐药的化疗药物仍然是当前抗肿瘤药物的开发与研究领域的焦点。鬼臼毒素是从小蘖科鬼臼属植物中提取分离得到的一种具有显著细胞毒作用的天然活性成分。近年来，本课题组一直在从事鬼臼毒素的结构改造及其活性探究工作，并且合成了大量具有高活性的鬼臼毒素衍生物。随着研究的深入，大批鬼臼毒素衍生物涌现出来。其中，依托泊苷(VP-16)和替尼

8、泊苷(VM-26)已经在临床广泛应用。但它们同样存在一些毒副作用。其衍生物TOP-53、NK-611、GL331和NPF已作为抗肿瘤新药已陆续进入临床研究。目的：为了得到毒副作用小，活性更好的抗肿瘤药物，对鬼臼毒素进行结构修饰，合成新的抗肿瘤鬼臼毒素衍生物。方法：1以鬼臼毒素