新型抗糖尿病铬(III)配合物的合成和生物活性及机理探究

doi:10.6023/A20070285

化学学报 ›› 2020, Vol. 78 ›› Issue (11): 1260-1267.DOI: 10.6023/A20070285 上一篇下一篇

研究论文

新型抗糖尿病铬(III)配合物的合成和生物活性及机理探究

董金龙^a,b, 沈腊珍^a, 文斌^a, 宋珍^a, 冯俊杰^a, 梁钢^c, 刘斌^b, 杨斌盛^b

a 太原师范学院化学系晋中 030619;
b 山西大学分子科学研究所化学生物学与分子工程教育部重点实验室太原 030006;
c 山西医科大学第一医院病理科太原 030001

投稿日期:2020-07-02 发布日期:2020-09-04
通讯作者: 董金龙, 杨斌盛 E-mail:dongjinlong20123@163.com;yangbs@sxu.edu.cn
基金资助:
项目受国家自然科学基金（Nos.21571117，21701121）、山西省自然科学基金（No.201801D121064）、山西高校科技项目（No.2019L0818）和太原师范学院大学生创新创业项目（No.CXCY1905）资助.

Synthesis of A Novel Anti-diabetes Chromium(III) Complex and Investigation of Its Biological Activity and Mechanism

Dong Jinlong^a,b, Shen Lazhen^a, Wen Bin^a, Song Zhen^a, Feng Junjie^a, Liang Gang^c, Liu Bin^b, Yang Binsheng^b

a Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, China;
b Institute of Molecular Science, Key Laboratory of Chemical Biology of Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, China;
c Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan 030001, China

Received:2020-07-02 Published:2020-09-04
Supported by:
Project supported by the the National Natural Science Foundation of China (Nos. 21571117, 21701121), the Natural Science Foundation of Shanxi Province (No. 201801D121064), the Science and Technology Innovation Project of Colleges and Universities in Shanxi Province (No. 2019L0818), and the Innovation Project for College Students in Shanxi Province (No. CXCY1905).

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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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董金龙, 沈腊珍, 文斌, 宋珍, 冯俊杰, 梁钢, 刘斌, 杨斌盛. 新型抗糖尿病铬(III)配合物的合成和生物活性及机理探究[J]. 化学学报, 2020, 78(11): 1260-1267.

Dong Jinlong, Shen Lazhen, Wen Bin, Song Zhen, Feng Junjie, Liang Gang, Liu Bin, Yang Binsheng. Synthesis of A Novel Anti-diabetes Chromium(III) Complex and Investigation of Its Biological Activity and Mechanism[J]. Acta Chimica Sinica, 2020, 78(11): 1260-1267.

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参考文献

[1] Yu, J. C.; Wang, J. Q.; Zhang, Y. Q.; Chen, G. J.; Mao, W.; Ye, Y. Q.; Kahkoska, A. R.; Buse, J. B.; Langer, R.; Gu, Z. Nat. Biomed. Eng. 2020, 4, 499.
[2] WilIiamson, R. M.; Price, J. F.; Glancy, S.; Perry, E.; Nee, L. D.; Hayes, P. C.; Frier, B. M.; Van Look, L. A. F.; Johnston, G. I.; Reynolds, R. M.; Mark, W. J. Diabetes Care. 2011, 34, 1139.
[3] Samuel, V. T.; Liu, Z. X.; Qu, X. Q.; Elder, B. D.; Bilz, S.; Befroy, D.; Romanelli, A. J.; Shulman, G. I. J. Biol. Chem. 2004, 279, 32345.
[4] Xu, B.; Broome, U.; Uzunel M.; Nava, S.; Ge, X. P.; Kumagai-Braesch, M.; Hultenby, K.; Christensson, B.; Ericzon, B.; Holgersson, J.; Sumitran-Holgersson, S. Am J. Pathol. 2003, 163, 1275.
[5] Farrell, G. C.; Chitmri, S.; Lau, G. K.; Sollano, J. D. J. Gastroen Hepatol. 2007, 22, 775.
[6] Hidenobu, S.; Tomoyo, N.; Yusuke, I.; Satoru, H.; Ryoma, N.; Makoto, O. Molecules 2019, 24, 3131.
[7] Evans, J. L.; Maddux, B. A.; Goldfine, I. D. Antioxid. Redox. Sign. 2005, 7, 1040.
[8] Pechova, A.; Pavlata, L. Vet Med. 2007, 52, 1.
[9] Hua, Y. A.; Clark, S.; Ren, J.; Sreejayan, N. J. Nutr. Biochem. 2012, 23, 313.
[10] Yang, X. P.; Palanichamy, K.; Ontko, A. C.; Rao, M. N. A.; Fang, C. X.; Ren, J.; Sreejayan, N. FEBS Lett. 2005, 579, 1458.
[11] Duan, W. S.; Liu, B.; Sun, Z. G.; Yang, B. S. Acta Chim. Sinica 2011, 69, 1789(in Chinese). (段文胜, 刘斌, 孙占国, 杨斌盛, 化学学报, 2011, 69, 1789.)
[12] Nan, J. X.; Liu, B.; Yang, B. S. Acta Chim. Sinica 2011, 69, 640(in Chinese). (南俊霞, 刘斌, 杨斌盛, 化学学报, 2011, 69, 640.)
[13] Liu, B.; Sun, Z. G.; Yang, B. S. Acta Chim. Sinica 2008, 66, 2353(in Chinese). (刘斌, 孙占国, 杨斌盛, 化学学报, 2008, 66, 2353.)
[14] Liu, B.; Li, Y. Q.; Yang, B. S. Acta Chim. Sinica 2006, 64, 917(in Chinese). (刘斌, 李英奇, 杨斌盛, 化学学报, 2006, 64, 917.)
[15] Cho, Y. M.; Merchant, C. E.; Kieffer, T. J. Pharmacol. Therapeut. 2012, 135, 247.
[16] Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination Compounds, Part B, 5th ed., Wiley, New York, 1997.
[17] Adam, A. M. A.; Sharshar, T.; Mohamed, M. A.; Ibrahim, O. B.; Refat, M. S. Spectrochim. Acta A 2015, 149, 323.
[18] Hamada, Y. Z.; Carlson, B. L.; Shank, J. T. Synth. React. Inorg. Met. Org. Chem. 2003, 33, 1425.
[19] Chen, J. M.; Hao, O. J. Crit. Rev. Env. Sci. Tec. 1998, 28, 219.
[20] Andersen, J. E. T. Anal. Chim. Acta 1998, 361, 125.
[21] Irma, M.; Aviva, L.; Lay, P. A. Angew. Chem. Int. Ed. 2004, 43, 4504.
[22] Levina, A.; Lay, P. A. Coord. Chem. Rev. 2005, 249, 281.
[23] Pettine, M.; Lanoce, T.; Liberatori, A.; Loreti, L. Anal. Chim. Acta 1988, 209, 315.
[24] Dong, J. L.; Liu, B.; Liang, G.; Yang, B. S. J. Coord. Chem. 2018, 4, 1526.
[25] Yang, B. S.; Yang, P. Chin. Sci. Bull. 1984, 29, 1066(in Chinese). (杨斌盛, 杨频, 科学通报, 1984, 29, 1066.)
[26] Shrivastava, H. Y.; Nair, B. U. J. Inorg. Biochem. 2004, 98, 991.

新型抗糖尿病铬(III)配合物的合成和生物活性及机理探究

Synthesis of A Novel Anti-diabetes Chromium(III) Complex and Investigation of Its Biological Activity and Mechanism

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