Synthesis And Molecular Docking Of Matrine Derivatives

Human health and life are still seriously threatened by cancer. In recent years, with the development of medical workers in the research of tumor mechanism, a number of tumor associated targets were explained, and the structure was determined. These researches promoted the development of anti-cancer drugs from simple cytotoxic drugs to target specific anticancer drug targeting direction. Matrine is an alkaloid with anti-tumor, anti-arrhythmic and anti-inflammatory efficacy. However, due to its low bioavailability, anti-tumor mechanism of matrine is not clear. And the anti-tumor target of matrine is not certain. Furthermore, the central nervous system toxic side effects and other shortcomings of matrine limited its clinical application.The reverse docking study was performed on the molecular operating environment Molecular Operating Environment (MOE). While matrine was treated as a ligand molecules of target protein,21 tumor associated protein targets were selected to explore the potential targets of the matrine. The Reverse molecular docking results shows that matrine has a better docking results with DNA topoisomerase I, Acetyl cholinesterase and tumor necrosis factor. These data indicated that they are most likely to be potential targets of the matrine anti-tumor effect.On the basis of reverse molecular docking, two series of matrine derivatives were design and screened. Focused on the potential target, results of virtual screening and targeted drug inhibitors, sixteen novel matrine derivatives were chosen and have good anti-tumor active with high selectivity. All compounds were synthesized. All structures of the new derivatives were confirmed by ~1H NMR, MS.