Synthesis, Characterization, and Biological Evaluations of 1,3,5-Triazine Derivatives of Metformin Cyclization with Berberine and Magnolol in the Presence of Sodium Methylate

Abstract

The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1–3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures of the target product 2 and the intermediate product 7b were reported for the first time. All target products were evaluated for their anti-inflammatory and antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all products showed excellent anti-inflammatory effects and anti-insulin resistance effects. Our studies indicated that new compounds 1–3 were found to be active against inflammation and insulin resistance.

A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

“…HFD combined with STZ injection is a common method to model obese T2DM. Excess weight gain, obesity, hyperglycemia, hyperlipidemia and insulin resistance are found in the model rats . In obese T2DM, abnormal lipid metabolism in WAT can cause lipid efflux, lipid deposition and adipose tissue inflammation, which is closely related to the occurrence and development of insulin resistance .…”

“…Excess weight gain, obesity, hyperglycemia, hyperlipidemia and insulin resistance are found in the model rats. 28,29 In obese T2DM, abnormal lipid metabolism in WAT can cause lipid efflux, lipid deposition and adipose tissue inflammation, which is closely related to the occurrence and development of insulin resistance. 30 In the present study, BMH473 demonstrated a significant lower body weight, blood glucose and lipid content in obese T2DM rats (Table 1 and Figure 2).…”

“…The design and synthesis of BMH473 has been completed in previous work. Thus, BMH473 was prepared according to our previously published protocol . Both structure and purity of the synthesized BMH473 were verified prior to the assessment of biological activity.…”

“…Thus, BMH473 was prepared according to our previously published protocol. 28 Both structure and purity of the synthesized BMH473 were verified prior to the assessment of biological activity. 1 H and 13 C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Avance 400 at room temperature, by using tetramethylsilane (as internal standard) and chloroform-d (as deuterated solvent…”

“…However, little information is available on the synthesis of novel compounds containing Metformin and Berberin derivatives. Our group has designed and synthesized the novel compound BMH473 . In this study, in vivo (high‐fat diet and streptozotocin‐induced obese T2DM rats) and in vitro (3T3‐L1 adipocytes) models were used to investigate the therapeutic effects of BMH473 on the regulation of lipid and glucose metabolism in T2DM.…”