10-羟基喜树碱衍生物的合成及其抗肿瘤活性的初步研究

Preliminary Research on Synthesis of 10-hydroxycamptothecine Derivative and Its Antineoplastic Activity

为提高10-羟基喜树碱在水中溶解性和稳定性,将其与丁二酸酐经酯化合成喜树碱衍生物—10,20(S)-O-二琥珀酰羟基喜树碱,所得衍生物经核磁共振氢谱表征,并用水浴搅拌法测定衍生物溶解度。采用MTT比色法检测衍生物对结肠癌细胞SW480的生长抑制,DNA片段化分析和Hoechst 33342染色检测其对结肠癌细胞株凋亡的影响。结果表明,衍生物在水中的溶解度(25℃)为2.3mg,比10-羟基喜树碱高21.8倍;肿瘤细胞的生长抑制作用呈剂量/时间依赖性,其半数抑制浓度(IC50值)为700nM;而琼脂糖凝胶电泳检测到典型的DNA梯状图谱,Hoechst 33342染色表明喜树碱类衍生物可诱导细胞凋亡。

To improve the water solubility and stability of 10-hydroxycamptothecine, this research pro- duces camptothecin derivative-10, 20（S）-O-disuccinyl hydroxycamptothecine by synthesizing it with suc cinic anhydride through esterification, represents the characteristics of the derivation with HNMR and measures the solubility of the derivative with water bath mixing method; detects the growth inhibition of colon cancer cell SW480 by the derivative with MTT colorimetric method; conducts DNA fragmentation analysis on and detects its influence on apoptosis of colon cancer cell line with Hoechst 33342 staining. The result shows that the water solubility（25℃） of the derivative is 2.3 mg, 21.8 times higher than that of 10- hydroxycamptothecine; the growth inhibition of tumour cell depends on dosage/time and its median inhibitory concentration（IC50 value） is 700 nM; agarose gel electrophoresis finds typical DNA scalariform pattern. Hoechst 33342 staining shows that camptothecine derivative can induce cell apoptosis.