發(fā)布時間：2018-05-04 01:29

  本文選題：喜樹堿衍生物 + 西佛堿　； 參考：《解放軍藥學(xué)學(xué)報》2016年03期

【摘要】：目的為尋找生物利用度更好、抗腫瘤活性更高的喜樹堿衍生物,設(shè)計新型喜樹堿衍生物。方法對7-乙基-10-羥基喜樹堿10位羥基進行化學(xué)結(jié)構(gòu)修飾,連接生物相容性較好的羧基、特異性基團西佛堿結(jié)構(gòu),并對化合物進行體外細胞毒性評價。結(jié)果共合成11個未見文獻報道的新化合物,其結(jié)構(gòu)經(jīng)1H-NMR及MS確證。體外細胞毒性評價表明:目標(biāo)化合物對SPCA-1、MCF-79的體外細胞毒性大多強于陽性對照藥物伊立替康。結(jié)論驗證了西佛堿結(jié)構(gòu)有助于提高喜樹堿抗腫瘤活性。初步構(gòu)效關(guān)系分析表明:羧烷基類化合物的活性隨直鏈脂肪酸的增長而增強。
[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.
【作者單位】： 軍事醫(yī)學(xué)科學(xué)院毒物藥物研究所;
【分類號】：R914

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本文編號：1841001