摘要
近年来,国内外糖尿病的患病人数都在以惊人的速度逐年增加,该病已列为继心脑血管、癌症之后的严重危害人类健康的第三大疾病。显然,对于糖尿病的防治已是迫在眉睫。经研究发现:无机钒盐及钒配合物具有很好的类胰岛素活性,目前已有少数钒配合物投入到临床试验阶段。因此,钒配合物的合成已成为研究糖尿病的热点之一。
本文设计合成了三种未见报道的钒配合物,对其进行了结构表征;同时研究了配合物在水溶液中的稳定性和脂溶性;并进行了蛋白质酪氨酸磷酸酯酶PTP1B筛选等活性实验,具体工作如下:
第一:设计合成了三种未见报道的新羟胺钒配合物,即草酸羟胺钒配合物和丙二酸羟胺钒配合物(外界分别为Na~+,K~+)。通过元素分析、热重分析和核磁共振光谱分析从而确定了配合物的基本组成;通过红外光谱和紫外光谱分析可知:配位前后特征吸收峰发生了明显的移动,初步确定配合物的合成。此外,我们对丙二酸羟胺钒配合物(外界分别为Na~+)进行了单晶衍射分析,确定了其结构为稍微扭曲的五角双锥,为今后羟胺钒配合物晶体结构的研究提供了参考价值。
第二:根据药物研究的要求,对新合成的配合物进行了一系列性能测试。(1)稳定性研究:选取三种不同的pH溶液,对新合成的羟胺钒配合物进行了稳定性测试。结果表明:配合物具有一定的稳定性,为其成为一种潜在的新药提供了前提条件。(2)脂溶性研究(即:分配系数的测定):测定钒配合物溶解在正辛醇/KRB(pH=7.4)生理缓冲溶液两相中的吸光度,根据公式计算得到其分配系数。结果表明:新合成的配合物具有一定的脂溶性,具备了药物研究的基本条件。(3)活性测试:进行了初步的蛋白酪氨酸磷酸酶PTP1B模型实验,结果发现:新配合物对PTP1B的抑制率均低于50%,对PTP1B的选择性和活性比较低。我们将对新合成的钒配合物进行其他相关活性测试,探寻其在抗肿瘤等领域中的药物作用。由于时间限制,这部分的研究工作仍在继续。
毋容置疑,我们所进行的一系列工作为钒配合物结构和性能的研究提供了有意义的参考。
Recently, the incidence of diabetic at home and abroad is rising rapidly each year. It has already become the third most seriousdisease after cardiovascular diseases and cancer. Obviously, preventing and curing diabetes mellitus is important task which has no time to delay. A great deal of investigations suggest that vanadic salts and vanadium complexes have good insulin activity. At present,some vanadium complexes have been applied in clinical studies. So the synthesis of vanadium complexes has been hotspot in the research ofdiabetes.
Three new vanadium complexes are designed and synthesized in this paper, characterizing their structure; researching their stability in aqueous solution and partition coefficient in the physiological buffer solution of n-Octanol /KRB; Screening Tests through PTP1B. so follow the details:
Firstly, three new vanadium complexes (vanadium hydroxylamido complexes of oxalic acid and vanadium hydroxylamido complexes of malonic acid (outside ion including Na~+,K~+) were synthesized. By using elemental analysis, TG and HNMR, the basic components of these complexes were identified. Through IR and UV-Vis, we know that the compounds were synthesized according to the moving of the absorption peak. We also determinded the structure of the vanadium hydroxylamido complexes of malonic acid (outside ion: K~+) throngh the XRDspectra, this will supply a certain significance to research the crystal structure of the vanadium hydroxylamido complexes.
Secondly,according to the request of the medicine, we did a series of aptitude tests.(l) the research of the stability: Selecting three different pH solution, we sthdied the stability in aqueous solution of the two kinds of vanadium complexes. It is found that thy have a certain stability in different pH solution, this will provide prerequisite for a kind of potential new drug. (2) Fat-soluble research(detecting the partition coefficient):We detected the absorbance of the two kinds of vanadium complexes in the physiological buffer solution of n-Octanol /KRB. According to the formula, we got their partition coefficient. The outcome of the experiment suggests that they have a certain partition coefficient in the physiological pH solution .So the compounds have a basic condition for the medicine research. (3) Active test: the two kinds of complexes were tested by the model of PTP1B.The outcome of experiment suggests that the inhibition ratio of the two complexes to PTP1B was below 50%, the choice of PTP1B was not strong enough. The new compounds will be researched in other active tests, for example, the antineoplastic research. Further research work and characterization are now in progress.
Undoubtedly, the paper that the systesis and characterization of the compounds will provide sense referance.
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