喜树碱衍生物的设计合成及活性评价

发布时间：2018-05-04 01:29

本文选题：喜树碱衍生物 + 西佛碱　；参考：《解放军药学学报》2016年03期

【摘要】：目的为寻找生物利用度更好、抗肿瘤活性更高的喜树碱衍生物,设计新型喜树碱衍生物。方法对7-乙基-10-羟基喜树碱10位羟基进行化学结构修饰,连接生物相容性较好的羧基、特异性基团西佛碱结构,并对化合物进行体外细胞毒性评价。结果共合成11个未见文献报道的新化合物,其结构经1H-NMR及MS确证。体外细胞毒性评价表明:目标化合物对SPCA-1、MCF-79的体外细胞毒性大多强于阳性对照药物伊立替康。结论验证了西佛碱结构有助于提高喜树碱抗肿瘤活性。初步构效关系分析表明:羧烷基类化合物的活性随直链脂肪酸的增长而增强。
[Abstract]:Objective to search for camptothecin derivatives with better bioavailability and higher anti-tumor activity, and to design new camptothecin derivatives. Methods the 10-hydroxyl group of 7-ethyl-10-hydroxycamptothecin was modified by chemical structure, and the carboxyl group with good biocompatibility and the specific group Schiff base structure were connected. The cytotoxicity of the compounds was evaluated in vitro. Results A total of 11 new compounds were synthesized and their structures were confirmed by 1H-NMR and MS. In vitro cytotoxicity evaluation showed that the cytotoxicity of the target compound to SPCA-1 + MCF-79 was mostly stronger than that of the positive control drug irinotecan. Conclusion Schiff's structure is helpful to enhance the anti-tumor activity of camptothecin. The preliminary structure-activity relationship analysis showed that the activity of carboxyalkyl compounds increased with the increase of straight chain fatty acids.
【作者单位】：军事医学科学院毒物药物研究所;
【分类号】：R914

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