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
1. [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. doi: 10.1038/s41551-019-0508-y
2. [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. doi: 10.2337/dc10-2229
3. [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. doi: 10.1074/jbc.M313478200
4. [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. doi: 10.1016/S0002-9440(10)63487-6
5. [5]
  Farrell, G. C.; Chitmri, S.; Lau, G. K.; Sollano, J. D. J. Gastroen Hepatol. 2007, 22, 775. doi: 10.1111/j.1440-1746.2007.05002.x
6. [6]
  Hidenobu, S.; Tomoyo, N.; Yusuke, I.; Satoru, H.; Ryoma, N.; Makoto, O. Molecules 2019, 24, 3131. doi: 10.3390/molecules24173131
7. [7]
  Evans, J. L.; Maddux, B. A.; Goldfine, I. D. Antioxid. Redox. Sign. 2005, 7, 1040. doi: 10.1089/ars.2005.7.1040
8. [8]
  Pechova, A.; Pavlata, L. Vet Med. 2007, 52, 1.
9. [9]
  Hua, Y. A.; Clark, S.; Ren, J.; Sreejayan, N. J. Nutr. Biochem. 2012, 23, 313. doi: 10.1016/j.jnutbio.2011.11.001
10. [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. doi: 10.1016/j.febslet.2005.01.049
11. [11]
  Duan, W. S.; Liu, B.; Sun, Z. G.; Yang, B. S. Acta Chim. Sinica 2011, 69, 1789(in Chinese).
12. [12]
  Nan, J. X.; Liu, B.; Yang, B. S. Acta Chim. Sinica 2011, 69, 640(in Chinese).
13. [13]
  Liu, B.; Sun, Z. G.; Yang, B. S. Acta Chim. Sinica 2008, 66, 2353(in Chinese).
14. [14]
  Liu, B.; Li, Y. Q.; Yang, B. S. Acta Chim. Sinica 2006, 64, 917(in Chinese).
15. [15]
  Cho, Y. M.; Merchant, C. E.; Kieffer, T. J. Pharmacol. Therapeut. 2012, 135, 247. doi: 10.1016/j.pharmthera.2012.05.009
16. [16]
  Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination Compounds, Part B, 5th ed., Wiley, New York, 1997.
17. [17]
  Adam, A. M. A.; Sharshar, T.; Mohamed, M. A.; Ibrahim, O. B.; Refat, M. S. Spectrochim. Acta A 2015, 149, 323. doi: 10.1016/j.saa.2015.04.115
18. [18]
  Hamada, Y. Z.; Carlson, B. L.; Shank, J. T. Synth. React. Inorg. Met. Org. Chem. 2003, 33, 1425. doi: 10.1081/SIM-120024320
19. [19]
  Chen, J. M.; Hao, O. J. Crit. Rev. Env. Sci. Tec. 1998, 28, 219. doi: 10.1080/10643389891254214
20. [20]
  Andersen, J. E. T. Anal. Chim. Acta 1998, 361, 125. doi: 10.1016/S0003-2670(98)00041-5
21. [21]
  Irma, M.; Aviva, L.; Lay, P. A. Angew. Chem. Int. Ed. 2004, 43, 4504. doi: 10.1002/anie.200460113
22. [22]
  Levina, A.; Lay, P. A. Coord. Chem. Rev. 2005, 249, 281. doi: 10.1016/j.ccr.2004.02.017
23. [23]
  Pettine, M.; Lanoce, T.; Liberatori, A.; Loreti, L. Anal. Chim. Acta 1988, 209, 315. doi: 10.1016/S0003-2670(00)84579-1
24. [24]
  Dong, J. L.; Liu, B.; Liang, G.; Yang, B. S. J. Coord. Chem. 2018, 4, 1526.
25. [25]
  Yang, B. S.; Yang, P. Chin. Sci. Bull. 1984, 29, 1066(in Chinese).
26. [26]
  Shrivastava, H. Y.; Nair, B. U. J. Inorg. Biochem. 2004, 98, 991. doi: 10.1016/j.jinorgbio.2004.02.014
1. [1]
  Haitang WANG , Yanni LING , Xiaqing MA , Yuxin CHEN , Rui ZHANG , Keyi WANG , Ying ZHANG , Wenmin WANG . Construction, crystal structures, and biological activities of two Ln^Ⅲ₃ complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1474-1482. doi: 10.11862/CJIC.20240188
2. [2]
  Xin MA , Ya SUN , Na SUN , Qian KANG , Jiajia ZHANG , Ruitao ZHU , Xiaoli GAO . A Tb₂ complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357
3. [3]
  Sirui Xin , Jiayin Zhou , Kin Shing Chan . Smelling Disease: E-nose. University Chemistry, 2024, 39(9): 141-145. doi: 10.3866/PKU.DXHX202309051
4. [4]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
5. [5]
  Linhan Tian , Changsheng Lu . Discussion on Sextuple Bonding in Diatomic Motifs of Chromium Family Elements. University Chemistry, 2024, 39(8): 395-402. doi: 10.3866/PKU.DXHX202401056
6. [6]
  Jianjun LI , Mingjie REN , Lili ZHANG , Lingling ZENG , Huiling WANG , Xiangwu MENG . UV-assisted degradation of tetracycline hydrochloride by MnFe₂O₄@activated carbon activated persulfate. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1869-1880. doi: 10.11862/CJIC.20240187
7. [7]
  Rong Tian , Yadi Yang , Naihao Lu . Comprehensive Experimental Design of Undergraduate Students Based on Interdisciplinarity: Study on the Effect of Quercetin on Chlorination Activity of Myeloperoxidase. University Chemistry, 2024, 39(8): 247-254. doi: 10.3866/PKU.DXHX202312064
8. [8]
  Quanliang Chen , Zhaohui Zhou . Research on the Active Site of Nitrogenase over Fifty Years. University Chemistry, 2024, 39(7): 287-293. doi: 10.3866/PKU.DXHX202310133
9. [9]
  Yukai Jiang , Yihan Wang , Yunkai Zhang , Yunping Wei , Ying Ma , Na Du . Characterization and Phase Diagram of Surfactant Lyotropic Liquid Crystal. University Chemistry, 2024, 39(4): 114-118. doi: 10.3866/PKU.DXHX202309033
10. [10]
  Xiaowei TANG , Shiquan XIAO , Jingwen SUN , Yu ZHU , Xiaoting CHEN , Haiyan ZHANG . A zinc complex for the detection of anthrax biomarker. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1850-1860. doi: 10.11862/CJIC.20240173
11. [11]
  Jianfeng Yan , Yating Xiao , Xin Zuo , Caixia Lin , Yaofeng Yuan . Comprehensive Chemistry Experimental Design of Ferrocenylphenyl Derivatives. University Chemistry, 2024, 39(4): 329-337. doi: 10.3866/PKU.DXHX202310005
12. [12]
  Zhibei Qu , Changxin Wang , Lei Li , Jiaze Li , Jun Zhang . Organoid-on-a-Chip for Drug Screening and the Inherent Biochemistry Principles. University Chemistry, 2024, 39(7): 278-286. doi: 10.3866/PKU.DXHX202311039
13. [13]
  Dan Li , Hui Xin , Xiaofeng Yi . Comprehensive Experimental Design on Ni-based Catalyst for Biofuel Production. University Chemistry, 2024, 39(8): 204-211. doi: 10.3866/PKU.DXHX202312046
14. [14]
  Yang Liu , Peng Chen , Lei Liu . Chemistry “101 Plan”: Design and Construction of Chemical Biology Textbook. University Chemistry, 2024, 39(10): 45-51. doi: 10.12461/PKU.DXHX202407085
15. [15]
  Tianyu Feng , Guifang Jia , Peng Zou , Jun Huang , Zhanxia Lü , Zhen Gao , Chu Wang . Construction of the Chemistry Biology Experiment Course in the Chemistry “101 Program”. University Chemistry, 2024, 39(10): 69-77. doi: 10.12461/PKU.DXHX202409002
16. [16]
  Lihui Jiang , Wanrong Dong , Hua Yang , Yongqing Xia , Hongjian Peng , Jun Yuan , Xiaoqian Hu , Zihan Zeng , Yingping Zou , Yiming Luo . Study on Extraction of p-Hydroxyacetophenone. University Chemistry, 2024, 39(11): 259-268. doi: 10.12461/PKU.DXHX202402056
17. [17]
  Jingjing QING , Fan HE , Zhihui LIU , Shuaipeng HOU , Ya LIU , Yifan JIANG , Mengting TAN , Lifang HE , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003
18. [18]
  Chunmei GUO , Weihan YIN , Jingyi SHI , Jianhang ZHAO , Ying CHEN , Quli FAN . Facile construction and peroxidase-like activity of single-atom platinum nanozyme. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1633-1639. doi: 10.11862/CJIC.20240162
19. [19]
  Congying Lu , Fei Zhong , Zhenyu Yuan , Shuaibing Li , Jiayao Li , Jiewen Liu , Xianyang Hu , Liqun Sun , Rui Li , Meijuan Hu . Experimental Improvement of Surfactant Interface Chemistry: An Integrated Design for the Fusion of Experiment and Simulation. University Chemistry, 2024, 39(3): 283-293. doi: 10.3866/PKU.DXHX202308097
20. [20]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(1028)
HTML views(275)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142