近年来人们对海藻寡糖的生物活性及其应用的研究发现，海藻寡糖具有促进生长、抗肿瘤、降血脂血糖、抗自由基氧化、免疫调节等活性。钒是生命体的一种必需微量元素，具有降血糖、类胰岛素、抗癌等作用。早在19世纪，钒的无机盐就被用于治疗贫血、营养不良、肺结核等疾病。由于无机钒的脂溶性差、毒性较高、副作用大等缺点限制了它的进一步应用，故研究者开始选择合适的有机配体，设计合成有机钒配合物来增加其生物利用度。癌症和糖尿病严重危害着人类的公共健康，对治疗癌症和糖尿病的药物的研究一直是全世界科研工作者的研究焦点。钒化合物不仅具有优良的抗糖尿病活性还有较好的抗癌作用，本文制备了四种未见报道的海藻寡糖钒配合物，对其结构进行了表征，并研究了其抗氧化、抗癌和抑制PTP1B酶的生物活性，主要工作包括：1、以不同分子量的褐藻寡糖、琼胶寡糖及羧甲基琼胶寡糖为原料设计合成4种海藻寡糖钒配合物，通过FT-IR、UV-vis对化合物进行表征，通过ICP-MS对海藻寡糖钒配合物中钒的含量进行测定。2、采用番红花红法测定海藻寡糖钒配合物对EDTANa2-Fe(II)-H2O2体系产生的羟基自由基的清除作用，采用DPPH体系测定其对DPPH自由基的清除作用。实验表明，海藻寡糖钒配合物的抗氧化活性与各自的配体相比，都有明显的提高。3、以不同浓度的海藻寡糖钒配合物作用于人肝癌细胞BEL-7402，72小时后采用磺酰罗丹明B蛋白染色法检测细胞增殖程度。研究发现，海藻寡糖钒配合物在16 ~ 4000 μg/mL浓度范围内对人肝癌细胞BEL-7402的增殖均有较好的抑制作用。4、研究海藻寡糖钒配合物抑制蛋白酪氨酸磷酸酶1B（PTP1B）的活性，测定了初筛浓度为80 μg/mL时不同海藻寡糖钒配合物对PTP1B的抑制率，筛选抑制率大于等于50％的样品继续测定其IC50值。结果表明，海藻寡糖钒配合物对PTP1B有明显的抑制作用，IC50值在6.1 ~ 61.0 μg/mL之间。; In recent years, the biological activities and practical significances of algae oligosaccharides were studied by many researchers all over the world, and they found that it show wide biological activities, involving antioxidant, anti-cancer, stimulation of endothelial cell growth and migration, anti-diabetic and immunity adjustment. Vanadium, a transitional metal element, is known to be essential for human-beings and animals, having several excellent chemical and biochemical properties, such as insulin-like, anti-diabetic and anti-cancer activities. The inorganic salt of vanadium was used to cure many diseases like anemia, malnutrition and tuberculosis. However, its low lipophilicity and evident side effects limit its further application. Therefore, researchers now are interest in finding appropriate ligand to synthetize oxovanadium complexes which can obviously improve its bioavailability.Diabetes and cancer are the major diseases that have been acutely impairing the health of the human beings. Thus, investigations of anti-diabetic and anti-cancer drugs are always the hot topic of research all the time. A lot of investigations suggest that vanadium complexes possess good insulin activity, anti-diabetic activity as well as anti-cancer activity. In this paper, four new vanadyl algae oligosaccharides complexes were designed and synthesized. Various methods have been used to character their structure. And their biological activities were also studied, such as antioxidant, anti-cancer and PTP1B enzyme inhibition activity. The main contents are as follow. 1. Four novel vanadyl algae oligosaccharides complexes were successfully synthesized with alginate oligosaccharides, agro-oligosaccharides or carboxymethyl agro-oligosaccharides as raw material. Infrared spectroscopy (IR) and UV-Vis spectroscopy were used to characterize the as-prepared complexes. And the amounts of V in the vanadyl algae oligosaccharides complexes were determined by inductively coupled plasma-mass spectrometry (ICP-MS). 2. The antioxidant activity of vanadyl algae oligosaccharides complexes was investigated by employing in vitro systems including hydroxyl and DPPH radical scavenging methods. The in vitro antioxidant results revealed that both the hydroxyl radical scavenging activity and the DPPH radical scavenging activity of oxovanadium algae oligosaccharides complexes were stronger than their ligands.3. The antiproliferative activities of vanadyl algae oligosaccharides complexes toward human hepatoma cell line BEL-7402 were studied by the SRB method (sulforhodamine B), and its results showed that all the vanadyl algae oligosaccharides complexes had the inhibitory effect on human hepatoma cell line BEL-7402 in vitro within 16 to 4000 μg/mL complexes concentrations.4. The suppression effects of 80 μg/mL vanadyl algae oligosaccharides complexes toward PTP1B enzyme were investigated. And we choosed part of the vanadyl algae oligosaccharides complexes which possessed inhibition rate of greater than 50% and their IC50 were measured. Its result demonstrated that vanadyl algae oligosaccharides complexes were the potent inhibitors to PTP1B with IC50 values (μg/mL) ranging from 6.1 to 61.0.
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