低分子量肝素乙酰化物的理化特性及其体外抗肿瘤活性研究

发布时间：2018-05-13 02:24

本文选题：低分子量肝素 + 化学修饰　；参考：《中国药理学通报》2015年01期

【摘要】：目的合成低抗凝血性低分子量肝素乙酰化物(ALMWH),并对其理化性质、抗肿瘤活性进行检测。方法采用高碘酸钠氧化,硼氢化钠还原法对普通肝素(UFH)进行选择性裂解,制得低抗凝血性低分子肝素(LMWH),以N,N二环己基碳二亚胺和二甲氨基吡啶(DCC/DMAP)为催化剂,对其进行乙酰化,制得ALMWH,经X线衍射(XRD)和差示扫描量热(DSC)试验,分析其构型和理化性质。以乳腺癌MDA-MB-231、MCF-7细胞为模型,检测其抗增殖、抗侵袭转移能力。利用家兔全血激活凝血时间实验(ACT)检测其抗凝血活性。结果 XRD测得ALMWH与LMWH同属无定形结构,但DSC热损失曲线和LMWH明显不同。与LMWH比较,ALMWH含有更多的结合水较低的抗凝血活性。更有意义的是,在低浓度下ALMWH即表现出较LMWH强的抗肿瘤细胞增殖、转移的活性。结论 ALMWH抗凝血活性低,具有一定的抗肿瘤增殖及侵袭转移的作用。本研究为低毒性抗肿瘤药物筛选提供了基础方法。
[Abstract]:Objective to synthesize a low anticoagulant low molecular weight heparin acetylated compound (ALMWHM) and to detect its physicochemical properties and anti-tumor activity. Methods the low anticoagulant low molecular weight heparin (LMWHH) was prepared by sodium periodate oxidation and sodium borohydride reduction method. The low anticoagulant low molecular weight heparin (LMWHH) was prepared and acetylated over the catalysts of N-dicyclohexyl carbodiimide and dimethylaminopyridine dimethylaminopyridine-dimethylaminopyridine (DCC-DMAPs). ALMWHs were prepared by X-ray diffraction (XRD) and differential scanning calorimetry (DSCC). The configuration and physicochemical properties of ALMWHs were analyzed. Breast cancer MDA-MB-231 MCF-7 cell model was used to detect its ability of anti-proliferation and anti-invasion and metastasis. The anticoagulant activity of rabbit whole blood activated coagulation time (ACTT) was measured. Results XRD showed that ALMWH and LMWH belonged to the same amorphous structure, but the curve of DSC heat loss was obviously different from that of LMWH. Compared with LMWH, ALMWH has more anticoagulant activity with lower binding water. More significantly, ALMWH showed stronger anti-tumor cell proliferation and metastasis activity than LMWH at low concentration. Conclusion ALMWH has low anticoagulant activity and has some anti-tumor proliferation and invasion and metastasis effects. This study provides a basic method for screening low-toxicity anti-tumor drugs.
【作者单位】：安徽省生化药物工程技术研究中心;蚌埠医学院药学系;蚌埠医学院第一附属医院心胸外科;
【基金】：国家自然科学基金资助项目(No 30972864) 安徽省教育厅自然科学研究重点项目(No KJ2012A202) 安徽省教育厅自然科学研究一般项目(No KJ2013B140)
【分类号】：R96

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