Citation: 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. doi: 10.6023/A20070285 shu

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

Corresponding author: Dong Jinlong, dongjinlong20123@163.com Yang Binsheng, yangbs@sxu.edu.cn
Received Date: 2 July 2020
Available Online: 3 September 2020
Fund Project: the Science and Technology Innovation Project of Colleges and Universities in Shanxi Province 2019L0818the Natural Science Foundation of Shanxi Province No. 201801D121064the the National Natural Science Foundation of China 21571117Project 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)the the National Natural Science Foundation of China 21701121the Innovation Project for College Students in Shanxi Province CXCY1905

Figures(11)

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.
- chromium(Ⅲ) phenformin,
- diabetes,
- biology activity,
- glucagon,
- toxicity
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