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

In order to search for novel anti-diabetes molecules, phenformin (Phf) was used as precursors to prepare chromium(III) complex [Cr(Phf)(3)]Cl-3 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 densib, 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) C in Phosphate Buffer Saline (PBS) buffer at pH 7.4 by fluorescence spectra, which the conditional binding constant K is 1.29x10(5) 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)]Cl-3 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.