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抗癌药物多西紫杉醇与人血清白蛋白化学交联药物的合成
发表时间：2017-12-15 浏览量：2190 下载量：517
| 全部作者： | 刘志国，彪林海 |
| 作者单位： | 东北林业大学森林植物生态学教育部重点实验室 |
| 摘 要： | 开发低毒和具有靶向性的新型紫杉烷类药物制剂是一个非常重要的研究课题。本研究探索多西紫杉醇与人血清白蛋白化学交联药物的合成。将多西紫杉醇的2’羟基位与人血清白蛋白34位半胱氨酸上的巯基处，通过5-己烯酸进行精确的共价交联。合成的中间产物和最终产物采用核磁共振波谱（nuclear magnetic resonance spectroscopy，NMR）和质谱（mass spectrometry，MS）进行鉴定和表征。人乳腺癌细胞MCF-7和人前列腺癌细胞PC3体外活性试验表明，这种交联产物在较低浓度时毒性较小，而在较高浓度时具有与多西紫杉醇相当或更强的活性。本研究结果对进一步开发新型紫杉烷类白蛋白化学共价交联药物制剂提供了一种新策略。 |
| 关 键 词： | 药物化学；多西紫杉醇；人血清白蛋白；5-己烯酸；化学交联药物 |
| Title： | Synthesis of a chemical conjugate of anticancer drug docetaxel with human serum albumin |
| Author： | LIU Zhiguo, BIAO Linhai |
| Organization： | Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University |
| Abstract： | Development of a new kind of formulation of docetaxel with low side effects and high targeting ability is a very important issue. In this paper, we explored the exact covalent linkage of docetaxel and human serum albumin (HSA) by one organic linker. 5-hexenoic acid was applied to exactly link the 2’ hydroxyl of docetaxel with the sulfydryl of the cysteine-34 of HSA to obtain docetaxel-albumin conjugate. The obtained intermediate and final conjugate were identified and characterized by nuclear magnetic resonance spetroscopy (NMR) and mass spectrometry (MS). The cytotoxicity of the docetaxel-HSA conjugate in vitro cell cytotoxicity experiments was relatively weak for human breast cancer cell line MCF-7 and human prostate cancer cell line PC3 at relatively low concentration whereas it became equal or more toxic in comparison to pure docetaxel with the higher concentration. The present result provided a new conjugation strategy for further development of new kinds of docetaxel-albumin prodrugs. |
| Key words： | medicinal chemistry; docetaxel; human serum albumin (HSA); 5-hexenoic acid; chemical conjugate |
| 发表期数： | 2017年12月第23期 |
| 引用格式： | 刘志国，彪林海. 抗癌药物多西紫杉醇与人血清白蛋白化学交联药物的合成[J]. 中国科技论文在线精品论文，2017，10（23）：2620-2627. |
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