摘要/Abstract
为了寻找新型的抗糖尿病分子，以苯乙双胍为前体，制备了苯乙双胍铬（III）配合物.通过元素分析、摩尔电导率、电喷雾质谱、红外光谱、紫外可见光谱和核磁共振波谱对配合物的结构进行了表征，并研究了配合物在不同温度、不同pH值下溶液的稳定性、与H2O2的反应性和形貌.同时，构建了糖尿病C57小鼠模型，研究了其生物活性和毒性.结果证明，配合物对其活性指标均有好的抑制作用，保留了苯乙双胍的降糖性质，对机体是无毒的，并且通过MTT（3-（4，5-二甲基噻唑-2）-2，5-二苯基四氮唑溴盐）实验说明配合物的生物相容性较好，实现了金属配合物降糖与控脂的多功能化应用.在此基础上，通过光谱法研究了配合物与胰高血糖素的相互作用，表明配合物对胰高血糖素是静态猝灭以较强的作用力结合，条件结合常数为1.29×105 L·mol-1，结合位点数约为1，初步提出了配合物的新的降糖机制.
关键词: 苯乙双胍铬, 糖尿病, 生物活性, 胰高血糖素, 毒性
In order to search for novel anti-diabetes molecules, phenformin (Phf) was used as precursors to prepare chromium(III) complex [Cr(Phf)3]Cl3 at room temperature. The complex was characterized by elemental analysis (EA), molar conductivity (MC), electrospray ionization mass spectrometry (ESI-MS), infrared (IR), UV-vis and NMR spectroscopy, respectively. In this work, the stability of complex solutions at different temperatures and pH values, reactivity with H2O2 were discussed in detail. The morphology and thermal studies of the complex were also investigated. Meanwhile, C57 diabetic mouse model induced by diet combined with streptozocin (STZ) was established to explore its biological activity from the aspects of fasting blood glucose (FBG), fasting serum insulin (FINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) levels, and oral toxicity. Afterwards, in order to explore the biological hypoglycemic mechanism of the complex, the interaction between the complex and glucagon was studied at (37±0.5) ℃ in Phosphate Buffer Saline (PBS) buffer at pH 7.4 by fluorescence spectra, which the conditional binding constant K is 1.29×105 L·mol-1, and the number of binding sites n is about 1. As a result, the interaction between the complex and glucagon was static quenching. The complex which retained the glucose-lowering properties of Phf exhibited good physical and chemical properties, beneficial function on blood glucose and lipid metabolism for Type II Diabetes mellitus (T2DM). The glucose-lowering mechanism of the complex was proposed, and the multi-functional application of metal complex in glucose-lowering and lipid-controlling was also achieved. Furthermore, oral toxicity results showed that the complex had no toxicity on all organs of mice. Methyl Thiazolyl Tetrazolium (MTT) assays also showed that the complex exhibited lower cytotoxicity than the positive control CrCl3 and Phf. Taken together, these results demonstrated that the non-toxic [Cr(Phf)3]Cl3 complex might be a potential candidate for novel anti–diabetic drug development. It may also provide a new idea for the prevention and treatment of type 2 diabetes.
Key words: chromium(III) phenformin, diabetes, biology activity, glucagon, toxicity
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