紫杉醇前药的合成及其对肿瘤细胞活性抑制的研究

Synthesis of Paclitaxel Prodrugs and the Activity of its Tumor Cells

选用肿瘤细胞生长过程中的必需氨基酸——谷氨酸,作为修饰紫杉醇的Linker,并用FITC标记谷氨酸-紫杉醇,对紫杉醇前药进行结构鉴定、释药动力学曲线、毒性和细胞摄取量进行了研究,实验结果表明:与紫杉醇原药相比谷氨酸-紫杉醇可提高其水溶性,并具有较好的释药动力学曲线,对乳腺癌MDA-MB-231具有良好的药效,为进一步合成具有靶向性紫杉醇前药打好基础。

Despite hope and promises paclitaxel(PTX) has engendered serious drawbacks which hamper PTX's clinical usefulness.The poor water solubility of PTX is another problem that significantly reduces its wider clinical application.To overcome these problems,a new active Linker-mediated Glu-PTX prodrug for tumor delivery has been developed.Fluorescent dye FITC is attached to Glu-PTX for in vitro optical imaging.The structure chemistry of the synthesized Glu-PTX and FITC-Glu-PTX-f product is evaluated by LC-MS study.